ClinVar Miner

Submissions for variant NM_001243279.3(ACSF3):c.689G>A (p.Trp230Ter)

gnomAD frequency: 0.00002  dbSNP: rs145583876
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795961 SCV000935443 pathogenic Combined malonic and methylmalonic acidemia 2024-03-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp230*) in the ACSF3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACSF3 are known to be pathogenic (PMID: 21841779, 26827111). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ACSF3-related conditions. ClinVar contains an entry for this variant (Variation ID: 642486). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000795961 SCV004213807 likely pathogenic Combined malonic and methylmalonic acidemia 2024-03-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000795961 SCV005077025 pathogenic Combined malonic and methylmalonic acidemia 2024-04-22 criteria provided, single submitter clinical testing Variant summary: ACSF3 c.689G>A (p.Trp230X) results in a premature termination codon, predicted to cause a absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 3.6e-05 in 251240 control chromosomes. c.689G>A has been reported in the literature in at-least one individual affected with Combined Malonic And Methylmalonic Aciduria (example, Imai-Okazaki_2019). 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 publications have been ascertained in the context of this evaluation (PMID: 30642647, 34900860). ClinVar contains an entry for this variant (Variation ID: 642486). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000795961 SCV002092413 pathogenic Combined malonic and methylmalonic acidemia 2021-06-25 no assertion criteria provided clinical testing

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