chr16-15771585-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_002474.3(MYH11):c.1017C>T(p.Ser339Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MYH11 | NM_002474.3 | c.1017C>T | p.Ser339Ser | synonymous_variant | Exon 9 of 41 | ENST00000300036.6 | NP_002465.1 | |
MYH11 | NM_001040113.2 | c.1038C>T | p.Ser346Ser | synonymous_variant | Exon 10 of 43 | ENST00000452625.7 | NP_001035202.1 | |
MYH11 | NM_001040114.2 | c.1038C>T | p.Ser346Ser | synonymous_variant | Exon 10 of 42 | NP_001035203.1 | ||
MYH11 | NM_022844.3 | c.1017C>T | p.Ser339Ser | synonymous_variant | Exon 9 of 42 | NP_074035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.1017C>T | p.Ser339Ser | synonymous_variant | Exon 9 of 41 | 1 | NM_002474.3 | ENSP00000300036.5 | ||
MYH11 | ENST00000452625.7 | c.1038C>T | p.Ser346Ser | synonymous_variant | Exon 10 of 43 | 1 | NM_001040113.2 | ENSP00000407821.2 |
Frequencies
GnomAD3 genomes AF: 0.000165 AC: 25AN: 151764Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.000255 AC: 64AN: 251472Hom.: 0 AF XY: 0.000235 AC XY: 32AN XY: 135910
GnomAD4 exome AF: 0.000163 AC: 238AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.000160 AC XY: 116AN XY: 727200
GnomAD4 genome AF: 0.000165 AC: 25AN: 151880Hom.: 0 Cov.: 29 AF XY: 0.0000808 AC XY: 6AN XY: 74214
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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MYH11: BP4, BP7 -
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Aortic aneurysm, familial thoracic 4 Uncertain:1Benign:1
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:2
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not specified Benign:1
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MYH11-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at