rs372378202
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001256545.2(MEGF10):c.1841-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,606,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001256545.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.1841-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.1841-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001256545.2 | P1 | |||
MEGF10 | ENST00000274473.6 | c.1841-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 | ||||
MEGF10 | ENST00000506709.1 | n.82-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000260 AC: 64AN: 246068Hom.: 0 AF XY: 0.000210 AC XY: 28AN XY: 133126
GnomAD4 exome AF: 0.000387 AC: 563AN: 1454576Hom.: 0 Cov.: 30 AF XY: 0.000366 AC XY: 265AN XY: 723468
GnomAD4 genome ? AF: 0.000308 AC: 47AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27AN XY: 74502
ClinVar
Submissions by phenotype
MEGF10-related myopathy Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at