rs749238106
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001256545.2(MEGF10):c.350G>A(p.Arg117His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000441 in 1,611,744 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. R117C) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.350G>A | p.Arg117His | missense_variant | 5/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.350G>A | p.Arg117His | missense_variant | 5/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.350G>A | p.Arg117His | missense_variant | 6/26 | 1 | P1 | ||
MEGF10 | ENST00000418761.6 | c.350G>A | p.Arg117His | missense_variant | 6/15 | 1 | |||
MEGF10 | ENST00000508365.5 | c.350G>A | p.Arg117His | missense_variant | 5/14 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152052Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000560 AC: 14AN: 249862Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135104
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1459692Hom.: 0 Cov.: 30 AF XY: 0.0000317 AC XY: 23AN XY: 726212
GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74244
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 117 of the MEGF10 protein (p.Arg117His). This variant is present in population databases (rs749238106, gnomAD 0.02%). 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: 565440). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MEGF10 protein function with a negative predictive value of 80%. 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