rs757715794
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001723.7(DST):c.3388G>A(p.Val1130Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001723.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.3388G>A | p.Val1130Met | missense_variant | 23/24 | ENST00000370765.11 | NP_001714.1 | |
DST | NM_001374736.1 | c.4929+3884G>A | intron_variant | ENST00000680361.1 | NP_001361665.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.3388G>A | p.Val1130Met | missense_variant | 23/24 | 1 | NM_001723.7 | ENSP00000359801.6 | ||
DST | ENST00000680361.1 | c.4929+3884G>A | intron_variant | NM_001374736.1 | ENSP00000505098.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250756Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135532
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461834Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 727216
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 26, 2021 | This sequence change replaces valine with methionine at codon 1130 of the DST protein (p.Val1130Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs757715794, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with DST-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at