rs149980738
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002474.3(MYH11):c.3531G>A(p.Thr1177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,614,226 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1177T) has been classified as Likely benign.
Frequency
Consequence
NM_002474.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.3531G>A | p.Thr1177= | synonymous_variant | 27/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.3552G>A | p.Thr1184= | synonymous_variant | 28/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.3552G>A | p.Thr1184= | synonymous_variant | 28/42 | ||
MYH11 | NM_022844.3 | c.3531G>A | p.Thr1177= | synonymous_variant | 27/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.3531G>A | p.Thr1177= | synonymous_variant | 27/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.3552G>A | p.Thr1184= | synonymous_variant | 28/43 | 1 | NM_001040113.2 | ||
ENST00000574212.1 | n.527C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000664 AC: 167AN: 251432Hom.: 4 AF XY: 0.000751 AC XY: 102AN XY: 135888
GnomAD4 exome AF: 0.000460 AC: 673AN: 1461892Hom.: 8 Cov.: 31 AF XY: 0.000554 AC XY: 403AN XY: 727248
GnomAD4 genome AF: 0.000282 AC: 43AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74494
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 | Jul 22, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 02, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | MYH11: BP4, BP7, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 02, 2016 | 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. - |
Aortic aneurysm, familial thoracic 4 Benign:2
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
MYH11-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 04, 2019 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at