rs771250421
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004006.3(DMD):āc.4300A>Gā(p.Lys1434Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000456 in 1,097,011 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K1434N) has been classified as Likely benign.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.4300A>G | p.Lys1434Glu | missense_variant | 31/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.4300A>G | p.Lys1434Glu | missense_variant | 31/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 exomes AF: 0.0000219 AC: 4AN: 182711Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67441
GnomAD4 exome AF: 0.00000456 AC: 5AN: 1097011Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 362523
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 19, 2019 | - - |
Duchenne muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2017 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in the literature in an individual affected with dilated cardiomyopathy (Invitae). This variant is present in population databases (rs771250421, ExAC 0.004%). This sequence change replaces lysine with glutamic acid at codon 1434 of the DMD protein (p.Lys1434Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at