rs587781052
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_002474.3(MYH11):c.3700G>A(p.Ala1234Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,613,080 control chromosomes in the GnomAD database, including 58,964 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_002474.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.3700G>A | p.Ala1234Thr | missense_variant | 28/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.3721G>A | p.Ala1241Thr | missense_variant | 29/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.3721G>A | p.Ala1241Thr | missense_variant | 29/42 | ||
MYH11 | NM_022844.3 | c.3700G>A | p.Ala1234Thr | missense_variant | 28/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.3700G>A | p.Ala1234Thr | missense_variant | 28/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.3721G>A | p.Ala1241Thr | missense_variant | 29/43 | 1 | NM_001040113.2 | ||
ENST00000574212.1 | n.327+6C>T | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.213 AC: 32222AN: 151472Hom.: 3880 Cov.: 30
GnomAD3 exomes AF: 0.247 AC: 61945AN: 251094Hom.: 8206 AF XY: 0.246 AC XY: 33328AN XY: 135742
GnomAD4 exome AF: 0.270 AC: 394158AN: 1461488Hom.: 55083 Cov.: 38 AF XY: 0.268 AC XY: 194872AN XY: 727068
GnomAD4 genome AF: 0.213 AC: 32222AN: 151592Hom.: 3881 Cov.: 30 AF XY: 0.212 AC XY: 15705AN XY: 74038
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:4
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 07, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Apr 08, 2019 | - - |
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 | 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 specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 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 | Ala1241Thr in exon 29 of MYH11: This variant is not expected to have clinical si gnificance because it has been identified in 26.2% (2253/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs16967494). - |
Aortic aneurysm, familial thoracic 4 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, 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 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Visceral myopathy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Lissencephaly, Recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 24, 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