chr4-127930752-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001371596.2(MFSD8):c.929G>A(p.Gly310Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G310A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001371596.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MFSD8 | NM_001371596.2 | c.929G>A | p.Gly310Asp | missense_variant | 9/12 | ENST00000641686.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MFSD8 | ENST00000641686.2 | c.929G>A | p.Gly310Asp | missense_variant | 9/12 | NM_001371596.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461312Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726934
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 7 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2009 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces glycine with aspartic acid at codon 310 of the MFSD8 protein (p.Gly310Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals with neuronal ceroid lipofuscinosis (PMID: 17564970, 19177532). ClinVar contains an entry for this variant (Variation ID: 1001). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Experimental studies have shown that this missense change does not substantially affect MFSD8 function (PMID: 17564970, 22668694). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at