rs772306149
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001256545.2(MEGF10):c.2050A>T(p.Ile684Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,614,024 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. I684T) 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.2050A>T | p.Ile684Phe | missense_variant | 16/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.2050A>T | p.Ile684Phe | missense_variant | 16/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.2050A>T | p.Ile684Phe | missense_variant | 17/26 | 1 | P1 | ||
MEGF10 | ENST00000506709.1 | n.291A>T | non_coding_transcript_exon_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251386Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135872
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461814Hom.: 0 Cov.: 30 AF XY: 0.0000371 AC XY: 27AN XY: 727194
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74358
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces isoleucine with phenylalanine at codon 684 of the MEGF10 protein (p.Ile684Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is present in population databases (rs772306149, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with MEGF10-related conditions. 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"). 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