chrX-140505047-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_005634.3(SOX3):c.14G>A(p.Arg5Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,203,988 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,306 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5P) has been classified as Likely benign.
Frequency
Consequence
NM_005634.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX3 | NM_005634.3 | c.14G>A | p.Arg5Gln | missense_variant | 1/1 | ENST00000370536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX3 | ENST00000370536.5 | c.14G>A | p.Arg5Gln | missense_variant | 1/1 | NM_005634.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00293 AC: 329AN: 112177Hom.: 0 Cov.: 23 AF XY: 0.00329 AC XY: 113AN XY: 34329
GnomAD3 exomes AF: 0.00286 AC: 467AN: 163377Hom.: 5 AF XY: 0.00290 AC XY: 160AN XY: 55159
GnomAD4 exome AF: 0.00325 AC: 3547AN: 1091765Hom.: 7 Cov.: 33 AF XY: 0.00333 AC XY: 1193AN XY: 358327
GnomAD4 genome ? AF: 0.00293 AC: 329AN: 112223Hom.: 0 Cov.: 23 AF XY: 0.00329 AC XY: 113AN XY: 34385
ClinVar
Submissions by phenotype
not provided Benign:6
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 13, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 30, 2014 | - - |
SOX3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 27, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Panhypopituitarism, X-linked;C2678223:Intellectual disability, X-linked, with panhypopituitarism Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 28, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at