rs201341211
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004006.3(DMD):c.1252A>T(p.Thr418Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,208,414 control chromosomes in the GnomAD database, including 1 homozygotes. There are 159 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T418P) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.1252A>T | p.Thr418Ser | missense_variant | 11/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.1252A>T | p.Thr418Ser | missense_variant | 11/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000251 AC: 28AN: 111733Hom.: 0 Cov.: 23 AF XY: 0.000265 AC XY: 9AN XY: 33927
GnomAD3 exomes AF: 0.000235 AC: 43AN: 183104Hom.: 0 AF XY: 0.000133 AC XY: 9AN XY: 67616
GnomAD4 exome AF: 0.000450 AC: 493AN: 1096681Hom.: 1 Cov.: 30 AF XY: 0.000414 AC XY: 150AN XY: 362107
GnomAD4 genome ? AF: 0.000251 AC: 28AN: 111733Hom.: 0 Cov.: 23 AF XY: 0.000265 AC XY: 9AN XY: 33927
ClinVar
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 02, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 15, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | DMD: BP4, BS1 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 05, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 18, 2016 | p.Thr418Ser in exon 11 of DMD: This variant is not expected to have clinical sig nificance because it was seen in 20/47913 European chromosomes, including 5 hem izygotes, by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs201341211) and due to a lack of conservation across species, includ ing mammals. Of note, >5 mammals (Ferret, Panda, Pacific Walrus, Weddell seal, M anatee, Armadillo, Platypus) have serine (Ser) at this position despite high nea rby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. - |
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 24, 2019 | - - |
Duchenne muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 13, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at