16-15721032-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4BP6
The NM_002474.3(MYH11):c.4598C>G(p.Ser1533Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,852 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1533F) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.4598C>G | p.Ser1533Cys | missense_variant | 33/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.4619C>G | p.Ser1540Cys | missense_variant | 34/43 | ENST00000452625.7 | |
NDE1 | NM_017668.3 | c.948-3159G>C | intron_variant | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.4598C>G | p.Ser1533Cys | missense_variant | 33/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.4619C>G | p.Ser1540Cys | missense_variant | 34/43 | 1 | NM_001040113.2 | ||
NDE1 | ENST00000396354.6 | c.948-3159G>C | intron_variant | 1 | NM_017668.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152050Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727212
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152050Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74264
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2018 | The p.S1533C variant (also known as c.4598C>G), located in coding exon 32 of the MYH11 gene, results from a C to G substitution at nucleotide position 4598. The serine at codon 1533 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species; however, cysteine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Aortic aneurysm, familial thoracic 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2019 | This sequence change replaces serine with cysteine at codon 1540 of the MYH11 protein (p.Ser1540Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 561305). This variant is not present in population databases (ExAC no frequency). - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at