Submissions for variant NM_005050.4(ABCD4):c.141G>C (p.Leu47Phe)

gnomAD frequency: 0.00038  dbSNP: rs147446660

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414128	SCV000491470	uncertain significance	not specified	2016-11-30	criteria provided, single submitter	clinical testing	The L47F variant in the ABCD4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L47F variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The L47F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret L47F as a variant of uncertain significance.
Invitae	RCV001034174	SCV001197504	likely benign	Methylmalonic acidemia with homocystinuria, type cblJ	2024-01-23	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV001034174	SCV001251917	likely benign	Methylmalonic acidemia with homocystinuria, type cblJ	2020-05-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002523924	SCV003691377	likely benign	Inborn genetic diseases	2021-10-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.