rs147770839
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_053025.4(MYLK):āc.842A>Gā(p.Lys281Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,566,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_053025.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.842A>G | p.Lys281Arg | missense_variant | 10/34 | ENST00000360304.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.842A>G | p.Lys281Arg | missense_variant | 10/34 | 5 | NM_053025.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000623 AC: 13AN: 208796Hom.: 0 AF XY: 0.0000356 AC XY: 4AN XY: 112512
GnomAD4 exome AF: 0.0000191 AC: 27AN: 1414650Hom.: 0 Cov.: 55 AF XY: 0.0000186 AC XY: 13AN XY: 700118
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74492
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 7 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 16, 2023 | - - |
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 30, 2021 | The p.K281R variant (also known as c.842A>G), located in coding exon 7 of the MYLK gene, results from an A to G substitution at nucleotide position 842. The lysine at codon 281 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#576135; Landrum et al., 2016) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at