chr16-15838241-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS1
The NM_002474.3(MYH11):c.12G>A(p.Lys4Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00082 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002474.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MYH11 | NM_002474.3 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 2 of 41 | ENST00000300036.6 | NP_002465.1 | |
MYH11 | NM_001040113.2 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 2 of 43 | ENST00000452625.7 | NP_001035202.1 | |
MYH11 | NM_001040114.2 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 2 of 42 | NP_001035203.1 | ||
MYH11 | NM_022844.3 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 2 of 42 | NP_074035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 2 of 41 | 1 | NM_002474.3 | ENSP00000300036.5 | ||
MYH11 | ENST00000452625.7 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 2 of 43 | 1 | NM_001040113.2 | ENSP00000407821.2 |
Frequencies
GnomAD3 genomes AF: 0.000578 AC: 88AN: 152154Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000582 AC: 145AN: 249178Hom.: 1 AF XY: 0.000630 AC XY: 85AN XY: 134890
GnomAD4 exome AF: 0.000845 AC: 1235AN: 1461860Hom.: 1 Cov.: 32 AF XY: 0.000798 AC XY: 580AN XY: 727240
GnomAD4 genome AF: 0.000578 AC: 88AN: 152272Hom.: 0 Cov.: 31 AF XY: 0.000564 AC XY: 42AN XY: 74452
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 4 Uncertain:1Benign:3
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. -
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Familial thoracic aortic aneurysm and aortic dissection Benign:3
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not provided Benign:3
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MYH11: BP4, BP7 -
not specified Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Connective tissue disorder Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at