rs1260392202
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_002437.5(MPV17):c.284G>A(p.Gly95Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. G95S) has been classified as Uncertain significance.
Frequency
Consequence
NM_002437.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPV17 | NM_002437.5 | c.284G>A | p.Gly95Asp | missense_variant | 5/8 | ENST00000380044.6 | |
MPV17 | XM_005264326.5 | c.284G>A | p.Gly95Asp | missense_variant | 5/8 | ||
MPV17 | XM_017004151.2 | c.236G>A | p.Gly79Asp | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPV17 | ENST00000380044.6 | c.284G>A | p.Gly95Asp | missense_variant | 5/8 | 1 | NM_002437.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251250Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135796
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461712Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727146
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Aug 13, 2019 | This variant is interpreted as a variant of uncertain significance for Mitochondrial DNA depletion syndrome 6, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PM1, PM3-supporting. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Dec 01, 2017 | The NM_012160.4:c.419T>C (NP_036292.2:p.Val140Ala) [GRCH38: NC_000006.12:g.98926570A>G] variant in FBXL4 gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG guideline. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 13 which is a recessive disorder. PP2:This is a missense variant in FBXL4 with a low rate of benign and high rate of pathogenic missense variations. PP3:Computational evidence/predictors indicate the variant has deleterious effect on FBXL4 structure, function, or protein-protein interaction. PP4:Patient's phenotype or family history is highly specific for FBXL4. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Likely Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at