Submissions for variant NM_022367.4(SEMA4A):c.1451G>C (p.Gly484Ala)

gnomAD frequency: 0.00062  dbSNP: rs148744804

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000732344	SCV000860293	uncertain significance	not provided	2018-03-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000732344	SCV001235156	uncertain significance	not provided	2024-01-14	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 484 of the SEMA4A protein (p.Gly484Ala). This variant is present in population databases (rs148744804, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of SEMA4A-related conditions (PMID: 32483926). ClinVar contains an entry for this variant (Variation ID: 596486). 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 not expected to disrupt SEMA4A protein function with a negative predictive value of 80%. 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.
Illumina Laboratory Services, Illumina	RCV001097618	SCV001253914	uncertain significance	Cone-rod dystrophy 10	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001097619	SCV001253915	uncertain significance	Retinitis pigmentosa	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001097618	SCV004048592	uncertain significance	Cone-rod dystrophy 10	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003338775	SCV004048593	uncertain significance	Retinitis pigmentosa 35	2023-04-11	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000732344	SCV005186949	uncertain significance	not provided		criteria provided, single submitter	not provided