chr3-123733085-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PP2PP3_ModerateBP6
The NM_053025.4(MYLK):c.1327C>A(p.Pro443Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,613,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic 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. P443S) has been classified as Likely benign.
Frequency
Consequence
NM_053025.4 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 |
---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.1327C>A | p.Pro443Thr | missense_variant | 11/34 | ENST00000360304.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.1327C>A | p.Pro443Thr | missense_variant | 11/34 | 5 | NM_053025.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249246Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134866
GnomAD4 exome AF: 0.000129 AC: 189AN: 1461638Hom.: 1 Cov.: 35 AF XY: 0.000103 AC XY: 75AN XY: 727082
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74430
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 23, 2024 | The p.P443T variant (also known as c.1327C>A), located in coding exon 8 of the MYLK gene, results from a C to A substitution at nucleotide position 1327. The proline at codon 443 is replaced by threonine, an amino acid with highly similar properties. This alteration has been reported in a sudden infant death syndrome (SIDS) cohort and a thoracic aortic aneurysm and dissection (TAAD) (Neubauer J et al. Eur J Hum Genet, 2017 Apr;25:404-409; Li J et al. Mol Genet Genomic Med, 2021 Oct;9:e1800). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 20, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 17, 2023 | BS1 - |
Aortic aneurysm, familial thoracic 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at