chr5-127396660-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001256545.2(MEGF10):c.541C>T(p.Arg181Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R181H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001256545.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.541C>T | p.Arg181Cys | missense_variant | 6/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.541C>T | p.Arg181Cys | missense_variant | 6/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.541C>T | p.Arg181Cys | missense_variant | 7/26 | 1 | P1 | ||
MEGF10 | ENST00000418761.6 | c.541C>T | p.Arg181Cys | missense_variant | 7/15 | 1 | |||
MEGF10 | ENST00000508365.5 | c.541C>T | p.Arg181Cys | missense_variant | 6/14 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251040Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135758
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461752Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727170
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 539963). This variant has not been reported in the literature in individuals affected with MEGF10-related conditions. This variant is present in population databases (rs764996899, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 181 of the MEGF10 protein (p.Arg181Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at