rs558332944
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_002474.3(MYH11):c.3712G>T(p.Gly1238Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1238R) has been classified as Uncertain significance.
Frequency
Consequence
NM_002474.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.3712G>T | p.Gly1238Trp | missense_variant | 28/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.3733G>T | p.Gly1245Trp | missense_variant | 29/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.3733G>T | p.Gly1245Trp | missense_variant | 29/42 | ||
MYH11 | NM_022844.3 | c.3712G>T | p.Gly1238Trp | missense_variant | 28/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.3712G>T | p.Gly1238Trp | missense_variant | 28/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.3733G>T | p.Gly1245Trp | missense_variant | 29/43 | 1 | NM_001040113.2 | ||
ENST00000574212.1 | n.321C>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251198Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135802
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459966Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726232
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 18, 2022 | This missense variant replaces glycine with tryptophan at codon 1245 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251198 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at