rs9840993
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_053025.4(MYLK):c.439C>T(p.Pro147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 1,613,666 control chromosomes in the GnomAD database, including 762,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_053025.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.439C>T | p.Pro147Ser | missense_variant | 7/34 | ENST00000360304.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.439C>T | p.Pro147Ser | missense_variant | 7/34 | 5 | NM_053025.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.885 AC: 134504AN: 151972Hom.: 61294 Cov.: 31
GnomAD3 exomes AF: 0.948 AC: 237916AN: 250870Hom.: 113805 AF XY: 0.954 AC XY: 129366AN XY: 135572
GnomAD4 exome AF: 0.977 AC: 1428507AN: 1461576Hom.: 700795 Cov.: 60 AF XY: 0.977 AC XY: 710333AN XY: 727040
GnomAD4 genome ? AF: 0.885 AC: 134547AN: 152090Hom.: 61300 Cov.: 31 AF XY: 0.886 AC XY: 65882AN XY: 74328
ClinVar
Submissions by phenotype
not specified Benign:7
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 22, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 02, 2014 | This is a RefSeq error. The reference base (c.439C) is the minor allele. This al lele (C) has been identified in 0.7% (61/8600) of European American chromosomes and 36% (1598/4406) of African American chromosomes by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; dbSNP rs9840993) and thus meets cr iteria to be classified as benign. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Aortic aneurysm, familial thoracic 7 Benign:4
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 30, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 12, 2016 | Variant summary: This c.439C>T affects a conserved nucleotide, resulting in amino acid change from Pro to Ser. 3/4 in-silico tools predict this variant to be benign. This variant was found in 114076/120782 control chromosomes from ExAC at a frequency of 0.9444785, which is more than 75557 times greater than the maximal expected frequency of a pathogenic allele (0.0000125) in this gene. This proves that this variant is a very common polymorphism. One clinical lab (via ClinVar) has classified this variant as benign. Taken together, this variant has been classified as Benign. - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 07, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Megacystis, microcolon, hypoperistalsis syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at