rs764044446
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001256545.2(MEGF10):āc.3409A>Gā(p.Ser1137Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. S1137S) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.3409A>G | p.Ser1137Gly | missense_variant | 25/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.3409A>G | p.Ser1137Gly | missense_variant | 25/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.3409A>G | p.Ser1137Gly | missense_variant | 26/26 | 1 | P1 | ||
MEGF10 | ENST00000515622.1 | n.433+1697A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249684Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134912
GnomAD4 exome Cov.: 32
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This variant is present in population databases (rs764044446, gnomAD 0.008%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 472743). This variant has not been reported in the literature in individuals affected with MEGF10-related conditions. This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1137 of the MEGF10 protein (p.Ser1137Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at