Skip to main content

Table 2 Patients with autosomal biallelically or X-linked inherited PTVs or Dmis variants in the 21 prioritized candidate genes

From: Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder

Gene Proband (gender) Type Location (hg19) Ref Alt GenBank No Functional effect Nucleotide change AA. alteration gnomAD allele frequency pLI Phenotypes in OMIM (Inheritance) ACMG
Autosomal genes (n = 8)
 ANO5# 14,640.p1 (M) Chet chr11:22,242,756 G A NM_213599 SP/Syn c.294G > A SP/p.A98A 0.0007 0 Gnathodiaphyseal dysplasia (AD); Miyoshi muscular dystrophy 3 (AR); Muscular dystrophy, limb-girdle, autosomal recessive 12 (AR) VUS
chr11: 22,294,441 C G NM_213599 Mis c.2141C > G p.T714S 0.0009 P
 ATAD3A* 14,517.p1 (M) Chet chr1:1,469,361 G A NM_001170535 Mis c.1670G > A p.R557H 0.0002 0 Harel-Yoon syndrome (AD, AR); Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (AR) VUS
chr1:1,469,380 G - NM_001170535 FS c.1689delG p.Q563Hfs*9 0 P
 ATG7 13,998.p1 (M) Chet chr3:11,389,351 G T NM_006395 SP/Mis c.1126G > T SP/p.G376C 5.58E-05 0   VUS
chr3:11,404,365 G A NM_006395 Mis c.1762G > A p.V588M 0.0001   VUS
 HIPK3 13,076.p1 (M) Homo chr11:33,374,639 T C NM_001048200 SP/Mis c.3110 T > C SP/p.V1037A 0.0008 0.28   VUS
I NTS4 14,051.p1 (M) Chet chr11:77,635,920 G A NM_033547 SG c.1390C > T p.R464X 1.23E-05 0   VUS
chr11:77,649,828 G A NM_033547 Mis c.1034C > T p.S345L 0.0004   VUS
 LLGL1 14,404.p1 (M) Homo chr17:18,138,154 G A NM_004140 SP/Mis c.907G > A SP/p.G303S 0.0009 0   VUS
 RFT1* 11,176.p1 (M) Chet chr3:53,133,472 T C NM_052859 Mis c.1133A > G p.Y378C 0.0005 0 Congenital disorder of glycosylation (AR) VUS
chr3:53,126,384 C NM_052859 SP c.1458 + 1G > - SP 4.53E-06 P
 VPS13B* 12,651.p1 (M) Chet chr8:100,829,780 G A NM_017890 Mis c.8185G > A p.G2729R 7.98E-06 0 Cohen syndrome (AR) LP
chr8:100,396,500 G A NM_017890 SG c.2889G > A p.W963X 0 P
X-linked genes (n = 13)
 AFF2* 14,096.p1 (M) Hem chrX:148,068,931 - C NM_001170628 FS c.2582dupC p.I863Hfs*6 0 1 Mental retardation, X-linked, FRAXE type (XLR) P
 APOO 14,187.p1 (M) Hem chrX:23,886,804 G A NM_024122 SP/Syn c.294C > T SP/p.D98D 0 0.6   VUS
 CCDC22* 12,325.p1 (M) Hem chrX:49,105,278 A C NM_014008 SP/Mis c.1432A > C SP/p.M478L 0 1 Ritscher-Schinzel syndrome 2 (XLR) LP
11,720.p1 (M) chrX:49,105,359 C T NM_014008 Mis c.1513C > T p.R505W 6.18E-05 LP
 CUL4B* 14,363.p1 (M) Hem chrX:119,708,407 A G NM_003588 SP/Syn c.66 T > C SP/p.G22G 0 1 Mental retardation, syndromic 15 (XLR) LP
 CYBB# 14,070.p1 (M) Hem chrX:37,664,420 A G NM_000397 SP/Mis c.1313A > G SP/p.K438R 4.39E-05 1 Chronic granulomatous disease, X linked (XLR); Immunodeficiency 34, mycobacteriosis (XLR) LP
 GRIPAP1 14,524.p1 (M) Hem chrX:48,837,828 C T NM_020137 SP/Syn c.1830G > A SP/p.A610A 0.0001 1   VUS
 HDAC8* 13,136.p1 (M) Hem chrX:71,694,562 G - NM_001166419 FS c.755delC p.P252Qfs 7.35E-05 0.98 Cornelia de Lange syndrome 5 (XLD) LP
 IL13RA1 11,167.p1 (M) Hem chrX:117,881,009 T G NM_001560 Mis c.321 T > G p.S107R 0 0.96   VUS
11,488.p1 (M) chrX:117,895,252 C T NM_001560 SP/Syn c.828C > T SP/p.Y276Y 2.48E-05   VUS
 MED12* 11,217.p1 (M) Hem chrX:70,343,445 G A NM_005120 SP/Mis c.1619G > A SP/p.R540H 1.33E-05 1 Lujan-Fryns syndrome (XLR), Ohdo syndrome(XLR), Opitz-Kaveggia syndrome (XLR) VUS
12,626.p1 (M) chrX:70,352,298 A G NM_005120 Mis c.4325A > G p.H1442R 0 LP
 RBMX* 13,063.p1 (M) Hem chrX:135,957,417 C T NM_002139 SP/Mis c.782G > A SP/p.S261N 0 0.83 Mental retardation, X-linked, syndromic 11, Shashi type (XLR) LP
 SLC38A5 14,423.p1 (M) Hem chrX:48,325,258 C T NM_033518 SP/Mis c.247G > A SP/p.A83T 0 0.98   VUS
 UBE2A* 12,440.p1 (M) Hem chrX:118,716,638 A T NM_003336 SP/Mis c.329A > T SP/p.Q110L 0 0.82 Mental retardation, X-linked syndromic, Nascimento-type (XLR) LP
 USP9X* 13,929.p1 (M) Hem chrX:40,982,891 A G NM_001039590 Mis c.10A > G p.T4A 1.52E-05 1 Mental retardation, X-linked 99(XLR); Mental retardation, X-linked 99, syndromic, female-restricted (XLD) LP
11,358.p1 (M) chrX:40,996,058 G A NM_001039590 SP/Mis c.437G > A SP/p.R146K 0 LP
12,628.p1 (M) chrX:41,012,318 G C NM_001039590 Mis c.1881G > C p.M627I 1.39E-05 LP
  1. Genes marked with * are implicated in neurodevelopmental disorders, and those marked with # are associated with other genetic disorders. The coding variants within ± 2 bp of the exon–intron boundary were defined as cryptic splice sites using ANNOVAR. All X-linked hemizygous inherited variants were analyzed in males. The reference sequence of a certain gene in the ClinVar database or the transcript with the highest expression in the human brain based on the GTEx database was selected to annotate the recessive inherited variants. AD, autosomal dominant; AR, autosomal recessive; Chet, compound heterozygous; Dmis, deleterious missense; F, female; FS, frameshift; Hem, hemizygous; Homo, homozygous; LP, likely pathogenic; M, male; Mis, missense; P, pathogenic; pLI, probability of loss-of-function intolerance; PTVs, protein-truncating variants; SG, stop-gain; SP, splicing; Syn, synonymous; XLD, X-linked dominant; XLR, X-linked recessive; VUS, variant of uncertain significance. The variants in known disease genes were interpreted according to ACMG guidelines and other variants were determined as VUSs. The variants in VPS13B were reported in a previous study [37]