NM_004006.3:c.3269A>T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_004006.3(DMD):c.3269A>T(p.Gln1090Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000519 in 1,193,583 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 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. Q1090H) 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 Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.3269A>T | p.Gln1090Leu | missense_variant | Exon 24 of 79 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
GnomAD3 genomes AF: 0.0000446 AC: 5AN: 111996Hom.: 0 Cov.: 22 AF XY: 0.0000293 AC XY: 1AN XY: 34140
GnomAD3 exomes AF: 0.0000710 AC: 13AN: 183136Hom.: 0 AF XY: 0.000103 AC XY: 7AN XY: 67698
GnomAD4 exome AF: 0.0000527 AC: 57AN: 1081533Hom.: 0 Cov.: 27 AF XY: 0.0000774 AC XY: 27AN XY: 348749
GnomAD4 genome AF: 0.0000446 AC: 5AN: 112050Hom.: 0 Cov.: 22 AF XY: 0.0000292 AC XY: 1AN XY: 34204
ClinVar
Submissions by phenotype
not provided Uncertain:1
- -
DMD-related disorder Uncertain:1
The DMD c.3269A>T variant is predicted to result in the amino acid substitution p.Gln1090Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-32482710-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
- -
Cardiovascular phenotype Benign:1
This alteration is classified as likely 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. -
Duchenne muscular dystrophy Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at