rs565304206
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001256545.2(MEGF10):c.2330G>A(p.Arg777His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,614,104 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. R777L) 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.2330G>A | p.Arg777His | missense_variant | 18/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.2330G>A | p.Arg777His | missense_variant | 18/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.2330G>A | p.Arg777His | missense_variant | 19/26 | 1 | P1 | ||
MEGF10 | ENST00000506709.1 | n.571G>A | non_coding_transcript_exon_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251370Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135842
GnomAD4 exome AF: 0.0000540 AC: 79AN: 1461782Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727194
GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74484
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 777 of the MEGF10 protein (p.Arg777His). This variant is present in population databases (rs565304206, 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: 522774). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Dec 03, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at