Submissions for variant NM_000183.3(HADHB):c.110-2324G>C

gnomAD frequency: 0.00004  dbSNP: rs764471823

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology	RCV001030799	SCV001190223	uncertain significance	Metabolic acidosis; Renal tubular acidosis; Rickets	2019-11-09	criteria provided, single submitter	clinical testing	Variations in the HADHB gene are known to cause autosomal recessive Trifunctional protein deficiency (MIM#609015) where persistant metabolic acidosis and lactic acidosis are seen in the patients, alongwith motor delay. This variant is present in publicly available databases like Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP at a low minor allele frequency (MAF<0.0001) in heterozygous state. The variant is also present in our in-house exome database at a low frequency (MAF<0.001) only in heterozygous state. The variant was not reported to OMIM, ClinVar and Human Genome Mutation Database (HGMD) in any other affected individuals. Predictions from different in-silico pathogenicity prediction programs are contradictory. Due to lack of enough evidence the variant has been classified as uncertain significance as per ACMG guidelines. This patient also harbor an another homozygous frameshift variant earlier reported by us (ClinVar Accession ID: VCV000694733.1).