rs1555551728
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_002474.3(MYH11):āc.4888G>Cā(p.Glu1630Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1630D) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.4888G>C | p.Glu1630Gln | missense_variant | 34/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.4909G>C | p.Glu1637Gln | missense_variant | 35/43 | ENST00000452625.7 | |
NDE1 | NM_017668.3 | c.948-3975C>G | intron_variant | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.4888G>C | p.Glu1630Gln | missense_variant | 34/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.4909G>C | p.Glu1637Gln | missense_variant | 35/43 | 1 | NM_001040113.2 | ||
NDE1 | ENST00000396354.6 | c.948-3975C>G | intron_variant | 1 | NM_017668.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74288
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
Aortic aneurysm, familial thoracic 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 04, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1637 of the MYH11 protein (p.Glu1637Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 465744). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at