rs34341838
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002474.3(MYH11):āc.792T>Cā(p.Tyr264=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 1,611,816 control chromosomes in the GnomAD database, including 1,344 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_002474.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.792T>C | p.Tyr264= | splice_region_variant, synonymous_variant | 8/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.813T>C | p.Tyr271= | splice_region_variant, synonymous_variant | 9/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.813T>C | p.Tyr271= | splice_region_variant, synonymous_variant | 9/42 | ||
MYH11 | NM_022844.3 | c.792T>C | p.Tyr264= | splice_region_variant, synonymous_variant | 8/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.792T>C | p.Tyr264= | splice_region_variant, synonymous_variant | 8/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.813T>C | p.Tyr271= | splice_region_variant, synonymous_variant | 9/43 | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0291 AC: 4432AN: 152088Hom.: 92 Cov.: 32
GnomAD3 exomes AF: 0.0292 AC: 7339AN: 251464Hom.: 169 AF XY: 0.0290 AC XY: 3940AN XY: 135902
GnomAD4 exome AF: 0.0371 AC: 54186AN: 1459610Hom.: 1252 Cov.: 30 AF XY: 0.0363 AC XY: 26377AN XY: 726284
GnomAD4 genome ? AF: 0.0291 AC: 4431AN: 152206Hom.: 92 Cov.: 32 AF XY: 0.0290 AC XY: 2161AN XY: 74424
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 4 Benign:5
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 10, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Nov 19, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 29, 2012 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 04, 2013 | Tyr271Tyr in exon 9 of MYH11: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.2% (364/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs34341838). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:3
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 09, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 25, 2015 | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 10, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 23, 2014 | This alteration is classified as 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