rs146388001
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1
The NM_002474.3(MYH11):c.3562C>T(p.Arg1188Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,614,208 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 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.3562C>T | p.Arg1188Trp | missense_variant | Exon 27 of 41 | ENST00000300036.6 | NP_002465.1 | |
MYH11 | NM_001040113.2 | c.3583C>T | p.Arg1195Trp | missense_variant | Exon 28 of 43 | ENST00000452625.7 | NP_001035202.1 | |
MYH11 | NM_001040114.2 | c.3583C>T | p.Arg1195Trp | missense_variant | Exon 28 of 42 | NP_001035203.1 | ||
MYH11 | NM_022844.3 | c.3562C>T | p.Arg1188Trp | missense_variant | Exon 27 of 42 | NP_074035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.3562C>T | p.Arg1188Trp | missense_variant | Exon 27 of 41 | 1 | NM_002474.3 | ENSP00000300036.5 | ||
MYH11 | ENST00000452625.7 | c.3583C>T | p.Arg1195Trp | missense_variant | Exon 28 of 43 | 1 | NM_001040113.2 | ENSP00000407821.2 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000175 AC: 44AN: 251448Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135896
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727248
GnomAD4 genome AF: 0.000144 AC: 22AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74472
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:2
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. -
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not provided Uncertain:1
Reported in a patient referred for thoracic aortic aneurysm, reported as R1195W due to the use of an alternate transcript (Overwater et al., 2018); however, no additional clinical information was provided; Reported in ClinVar (ClinVar Variant ID# 201064; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29907982, 28659821) -
not specified Benign:1
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Aortic aneurysm, familial thoracic 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at