rs770202940
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_004006.3(DMD):c.1159A>G(p.Met387Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,208,621 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 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. M387R) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.1159A>G | p.Met387Val | missense_variant | 11/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.1159A>G | p.Met387Val | missense_variant | 11/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000360 AC: 4AN: 111253Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1AN XY: 33449
GnomAD3 exomes AF: 0.0000328 AC: 6AN: 182860Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67488
GnomAD4 exome AF: 0.0000629 AC: 69AN: 1097368Hom.: 0 Cov.: 30 AF XY: 0.0000579 AC XY: 21AN XY: 362832
GnomAD4 genome ? AF: 0.0000360 AC: 4AN: 111253Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1AN XY: 33449
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 14, 2016 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 06, 2017 | The p.Met387Val variant has not been previously reported in individuals with myo pathy, but has been reported in ClinVar (Variation ID# 239598). This variant has been identified in 6/90307 European chromosomes, including one hemizygote, by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs770202940). The affected amino acid is not well conserved in evolution with 5 fish species carrying a valine (Val), but computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Met387Val variant is uncertain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2023 | The p.M387V variant (also known as c.1159A>G), located in coding exon 11 of the DMD gene, results from an A to G substitution at nucleotide position 1159. The methionine at codon 387 is replaced by valine, an amino acid with highly similar properties. Based on data from gnomAD, the G allele has an overall frequency of <0.01% (8/204746) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was <0.01% (8/92345) of European (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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at