3-123734196-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_053025.4(MYLK):c.800C>A(p.Thr267Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,543,152 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
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.800C>A | p.Thr267Asn | missense_variant | 10/34 | ENST00000360304.8 | NP_444253.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.800C>A | p.Thr267Asn | missense_variant | 10/34 | 5 | NM_053025.4 | ENSP00000353452.3 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151624Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000156 AC: 3AN: 192284Hom.: 0 AF XY: 0.00000974 AC XY: 1AN XY: 102672
GnomAD4 exome AF: 0.0000108 AC: 15AN: 1391528Hom.: 0 Cov.: 53 AF XY: 0.0000116 AC XY: 8AN XY: 687010
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151624Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74032
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 09, 2023 | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 267 of the MYLK protein (p.Thr267Asn). This variant is present in population databases (rs755451013, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 547553). 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 MYLK protein function with a negative predictive value of 95%. 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. - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2021 | The p.T267N variant (also known as c.800C>A), located in coding exon 7 of the MYLK gene, results from a C to A substitution at nucleotide position 800. The threonine at codon 267 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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. - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at