5-127396631-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001256545.2(MEGF10):c.512C>T(p.Ala171Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. A171T) 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.512C>T | p.Ala171Val | missense_variant | 6/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.512C>T | p.Ala171Val | missense_variant | 6/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.512C>T | p.Ala171Val | missense_variant | 7/26 | 1 | P1 | ||
MEGF10 | ENST00000418761.6 | c.512C>T | p.Ala171Val | missense_variant | 7/15 | 1 | |||
MEGF10 | ENST00000508365.5 | c.512C>T | p.Ala171Val | missense_variant | 6/14 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000559 AC: 14AN: 250228Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135408
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461572Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727080
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74494
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 15, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 171 of the MEGF10 protein (p.Ala171Val). This variant is present in population databases (rs201824269, gnomAD 0.01%). 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: 350639). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | The c.512C>T (p.A171V) alteration is located in exon 7 (coding exon 5) of the MEGF10 gene. This alteration results from a C to T substitution at nucleotide position 512, causing the alanine (A) at amino acid position 171 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at