rs1800271
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_004006.3(DMD):āc.5459A>Gā(p.Asn1820Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000029 in 1,207,915 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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. N1820K) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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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.5459A>G | p.Asn1820Ser | missense_variant | 39/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.5459A>G | p.Asn1820Ser | missense_variant | 39/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000269 AC: 3AN: 111553Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33765
GnomAD3 exomes AF: 0.0000493 AC: 9AN: 182449Hom.: 0 AF XY: 0.0000595 AC XY: 4AN XY: 67251
GnomAD4 exome AF: 0.0000292 AC: 32AN: 1096362Hom.: 0 Cov.: 30 AF XY: 0.0000331 AC XY: 12AN XY: 362464
GnomAD4 genome AF: 0.0000269 AC: 3AN: 111553Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33765
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2022 | The p.N1820S variant (also known as c.5459A>G), located in coding exon 39 of the DMD gene, results from an A to G substitution at nucleotide position 5459. The asparagine at codon 1820 is replaced by serine, an amino acid with highly similar properties. This alteration has been reported in an ostensibly healthy cohort (Vojinovic D et al. Eur J Hum Genet, 2015 Jun;23:837-43). Based on data from gnomAD, the G allele has an overall frequency of <0.01% (9/182449) total alleles studied, with 4 hemizygote(s) observed. The highest observed frequency was <0.01% (8/81342) of Eurpoean (non-Finnish) alleles. This amino acid position is 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;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 15, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | DMD: BS2 - |
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at