Submissions for variant NM_001042472.3(ABHD12):c.103C>T (p.Arg35Cys)

gnomAD frequency: 0.00050  dbSNP: rs749409983

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001615720	SCV001835875	benign	not provided	2019-12-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001615720	SCV002180070	uncertain significance	not provided	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 35 of the ABHD12 protein (p.Arg35Cys). 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 ABHD12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1226455). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics	RCV002538501	SCV003689705	uncertain significance	Inborn genetic diseases	2021-08-18	criteria provided, single submitter	clinical testing	The c.103C>T (p.R35C) alteration is located in exon 1 (coding exon 1) of the ABHD12 gene. This alteration results from a C to T substitution at nucleotide position 103, causing the arginine (R) at amino acid position 35 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003405739	SCV004116003	uncertain significance	ABHD12-related disorder	2023-02-09	criteria provided, single submitter	clinical testing	The ABHD12 c.103C>T variant is predicted to result in the amino acid substitution p.Arg35Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.10% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-25371237-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Clinical Genetics, Academic Medical Center	RCV001615720	SCV001924415	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001615720	SCV001972418	uncertain significance	not provided		no assertion criteria provided	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815581	SCV005069336	uncertain significance	Optic atrophy	2022-01-01	no assertion criteria provided	clinical testing