rs150095036
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001256545.2(MEGF10):c.2477C>T(p.Ala826Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A826A) has been classified as Likely benign.
Frequency
Consequence
NM_001256545.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.2477C>T | p.Ala826Val | missense_variant | 19/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.2477C>T | p.Ala826Val | missense_variant | 19/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.2477C>T | p.Ala826Val | missense_variant | 20/26 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000439 AC: 11AN: 250666Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135454
GnomAD4 exome AF: 0.0000883 AC: 129AN: 1460642Hom.: 0 Cov.: 30 AF XY: 0.0000881 AC XY: 64AN XY: 726602
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 826 of the MEGF10 protein (p.Ala826Val). This variant is present in population databases (rs150095036, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MEGF10-related conditions. ClinVar contains an entry for this variant (Variation ID: 539960). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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