ClinVar Miner

Submissions for variant NM_001243279.3(ACSF3):c.1073C>T (p.Thr358Ile)

dbSNP: rs387907120
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000024135 SCV003275912 uncertain significance Combined malonic and methylmalonic acidemia 2022-11-29 criteria provided, single submitter clinical testing 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. 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 ACSF3 protein function. ClinVar contains an entry for this variant (Variation ID: 31139). This missense change has been observed in individual(s) with combined malonic and methylmalonic aciduria (PMID: 21841779). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 358 of the ACSF3 protein (p.Thr358Ile).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004689427 SCV005184441 uncertain significance not specified 2024-05-29 criteria provided, single submitter clinical testing Variant summary: ACSF3 c.1073C>T (p.Thr358Ile) results in a non-conservative amino acid change located in the AMP-dependent synthetase/ligase domain (IPR000873) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250810 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1073C>T has been reported in the literature in at least one individual affected with Combined Malonic And Methylmalonic Aciduria (Sloan_2011). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 21841779). ClinVar contains an entry for this variant (Variation ID: 31139). Based on the evidence outlined above, the variant was classified as uncertain significance.
OMIM RCV000024135 SCV000045426 pathogenic Combined malonic and methylmalonic acidemia 2011-08-14 no assertion criteria provided literature only

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