rs151150099
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_004006.3(DMD):c.3805C>T(p.His1269Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000274 in 1,205,019 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign 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. H1269P) 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 -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.3805C>T | p.His1269Tyr | missense_variant | 28/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.3805C>T | p.His1269Tyr | missense_variant | 28/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000126 AC: 14AN: 111307Hom.: 0 Cov.: 23 AF XY: 0.000149 AC XY: 5AN XY: 33667
GnomAD3 exomes AF: 0.0000383 AC: 7AN: 182584Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67362
GnomAD4 exome AF: 0.0000174 AC: 19AN: 1093712Hom.: 0 Cov.: 29 AF XY: 0.00000833 AC XY: 3AN XY: 359978
GnomAD4 genome ? AF: 0.000126 AC: 14AN: 111307Hom.: 0 Cov.: 23 AF XY: 0.000149 AC XY: 5AN XY: 33667
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 19, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 08, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 24, 2015 | The p.His1269Tyr variant in DMD has not been previously reported in individuals with cardiomyopathy, but has been identified in 4/8368 African chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs15 1150099). Computational prediction tools and conservation analysis do not provid e strong support for or against an impact to the protein. Computational splicing tools suggest this variant may lead to the creation of a novel 5' splice site; however, this information is not predictive enough to determine pathogenicity. I n summary, the clinical significance of the p.His1269Tyr variant is uncertain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2023 | The p.H1269Y variant (also known as c.3805C>T), located in coding exon 28 of the DMD gene, results from a C to T substitution at nucleotide position 3805. The histidine at codon 1269 is replaced by tyrosine, an amino acid with similar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.0049% (10/204406) total alleles studied, with 2 hemizygote(s) observed. The highest observed frequency was 0.0474% (9/19003) of African alleles. 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. - |
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at