rs775115784
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004006.3(DMD):āc.1382A>Gā(p.Asn461Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,205,126 control chromosomes in the GnomAD database, including 1 homozygotes. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N461N) has been classified as Likely benign.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.1382A>G | p.Asn461Ser | missense_variant | 12/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.1382A>G | p.Asn461Ser | missense_variant | 12/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000180 AC: 2AN: 110812Hom.: 0 Cov.: 22 AF XY: 0.0000301 AC XY: 1AN XY: 33170
GnomAD3 exomes AF: 0.0000220 AC: 4AN: 181760Hom.: 0 AF XY: 0.0000150 AC XY: 1AN XY: 66776
GnomAD4 exome AF: 0.0000128 AC: 14AN: 1094314Hom.: 1 Cov.: 29 AF XY: 0.0000166 AC XY: 6AN XY: 360714
GnomAD4 genome ? AF: 0.0000180 AC: 2AN: 110812Hom.: 0 Cov.: 22 AF XY: 0.0000301 AC XY: 1AN XY: 33170
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 11, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2022 | The p.N461S variant (also known as c.1382A>G), located in coding exon 12 of the DMD gene, results from an A to G substitution at nucleotide position 1382. The asparagine at codon 461 is replaced by serine, an amino acid with highly similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.0025% (5/203428) total alleles studied, with 2 hemizygote(s) observed. The highest observed frequency was 0.0339% (5/14745) of East Asian 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. - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Apr 04, 2017 | - - |
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at