ClinVar

Description

A homozygous deletion of exon 1 in MFSD8 (NM_001371596.2) was identified by exome sequencing in one individual with neuronal ceroid lipofuscinosis ([GRCh 38] chr4:127964562_127965767x0). These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoints. Inheritance information is unavailable. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. This intragenic variant deletes the first coding exon and is predicted to cause loss of the methionine initiation codon. This alteration is then predicted to lead to a truncated or absent protein. There is potential for rescue from a downstream methionine initiation codon. Loss of function of MFSD8 is an established disease mechanism in autosomal recessive neuronal ceroid lipofuscinosis (https://search.clinicalgenome.org/kb/gene-dosage). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.45 points, A: 0 points, 4-5: 0.15 points; Total: 0.6 points; Riggs 2020 (PMID: 31690835).