ClinVar Miner

Submissions for variant NM_005050.4(ABCD4):c.956A>G (p.Tyr319Cys)

gnomAD frequency: 0.00009  dbSNP: rs201777056
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000030859 SCV001389587 uncertain significance Methylmalonic acidemia with homocystinuria, type cblJ 2021-08-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265570 SCV002548357 likely pathogenic Cobalamin C disease 2022-05-26 criteria provided, single submitter clinical testing Variant summary: ABCD4 c.956A>G (p.Tyr319Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251364 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.956A>G has been reported in the literature in the compound heterozygous state in an individual who was affected with Methylmalonic Acidemia With Homocystinuria (Coelho_2012). In vitro experiments suggest that the variant does not impact protein localization, but that ATPase and cobalamin transport activities are lost compared to the wild-type ABCD4 protein (Kitai_2021). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000030859 SCV005635718 likely pathogenic Methylmalonic acidemia with homocystinuria, type cblJ 2024-01-09 criteria provided, single submitter clinical testing
OMIM RCV000030859 SCV000053534 pathogenic Methylmalonic acidemia with homocystinuria, type cblJ 2012-10-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000059785 SCV000091355 not provided not provided no assertion provided not provided

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