20-46725967-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_030777.4(SLC2A10):c.931G>A(p.Val311Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,613,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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_030777.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A10 | NM_030777.4 | c.931G>A | p.Val311Ile | missense_variant | 2/5 | ENST00000359271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271.4 | c.931G>A | p.Val311Ile | missense_variant | 2/5 | 1 | NM_030777.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000303 AC: 76AN: 250954Hom.: 0 AF XY: 0.000310 AC XY: 42AN XY: 135702
GnomAD4 exome AF: 0.000235 AC: 343AN: 1461468Hom.: 1 Cov.: 33 AF XY: 0.000241 AC XY: 175AN XY: 727048
GnomAD4 genome AF: 0.000243 AC: 37AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74478
ClinVar
Submissions by phenotype
Arterial tortuosity syndrome Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 13, 2021 | The SLC2A10 c.931G>A; p.Val311Ile variant (rs139932041), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 213720). This variant is found in the general population with an overall allele frequency of 0.029% (81/282,340 alleles) in the Genome Aggregation Database. The valine at codon 311 is moderately conserved, but computational analyses predict that this variant is neutral (REVEL: 0.14). Due to limited information, the clinical significance of the p.Val311Ile variant is uncertain at this time. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 28, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Reported in patients with pulmonary arterial hypertension or with familial intracranial aneurysms (Abou Hassan et al., 2018; Song et al., 2022); This variant is associated with the following publications: (PMID: 34668355, 29843651) - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 05, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2024 | This alteration is classified as likely 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at