ClinVar Miner

Submissions for variant NM_022367.4(SEMA4A):c.1123C>T (p.Arg375Trp)

gnomAD frequency: 0.00004  dbSNP: rs201094714
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153933 SCV000203550 uncertain significance not provided 2014-04-25 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000339071 SCV000348986 uncertain significance Retinitis Pigmentosa, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000401576 SCV000348987 uncertain significance Cone-rod dystrophy 10 2018-01-12 criteria provided, single submitter clinical testing 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.
Illumina Laboratory Services, Illumina RCV001101273 SCV001257873 uncertain significance Retinitis pigmentosa 2018-01-12 criteria provided, single submitter clinical testing 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000153933 SCV002955866 uncertain significance not provided 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 375 of the SEMA4A protein (p.Arg375Trp). This variant is present in population databases (rs201094714, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SEMA4A-related conditions. ClinVar contains an entry for this variant (Variation ID: 167672). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SEMA4A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV000401576 SCV004050537 uncertain significance Cone-rod dystrophy 10 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003343658 SCV004050538 uncertain significance Retinitis pigmentosa 35 2023-04-11 criteria provided, single submitter clinical testing

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