rs200361128
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_005634.3(SOX3):āc.157G>Cā(p.Val53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,182,238 control chromosomes in the GnomAD database, including 12 homozygotes. There are 1,075 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005634.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX3 | NM_005634.3 | c.157G>C | p.Val53Leu | missense_variant | 1/1 | ENST00000370536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX3 | ENST00000370536.5 | c.157G>C | p.Val53Leu | missense_variant | 1/1 | NM_005634.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00411 AC: 464AN: 112870Hom.: 1 Cov.: 24 AF XY: 0.00574 AC XY: 201AN XY: 35034
GnomAD3 exomes AF: 0.00744 AC: 951AN: 127771Hom.: 5 AF XY: 0.00696 AC XY: 282AN XY: 40527
GnomAD4 exome AF: 0.00257 AC: 2751AN: 1069324Hom.: 11 Cov.: 33 AF XY: 0.00251 AC XY: 875AN XY: 348464
GnomAD4 genome ? AF: 0.00411 AC: 464AN: 112914Hom.: 1 Cov.: 24 AF XY: 0.00570 AC XY: 200AN XY: 35088
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 29, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 18, 2023 | The p.Val53Leu variant in SOX3 is classified as benign because it has been identified in 2.1% of African/African American chromosomes, including 1 homozygote, in gnomAD (http://gnomad.broadinstitute.org, v.3.1.2), which is higher than expected for a disease causing variant in SOX3. ACMG/AMP Criteria applied: BA1. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 18, 2019 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Abnormal brain morphology Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
Intellectual disability, X-linked, with panhypopituitarism Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Jul 17, 2023 | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is out of keeping with known incidence of intellectual developmental disorder, X-linked, with isolated growth hormone deficiency, with more than 300 hemizygous alleles in gnomAD v2 (MIM#300123). (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
History of neurodevelopmental disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2012 | This alteration is classified as benign based on a combination of the following: 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at