rs201866780
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001723.7(DST):c.26G>T(p.Arg9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9C) has been classified as Likely benign.
Frequency
Consequence
NM_001723.7 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.26G>T | p.Arg9Leu | missense_variant | 1/24 | ENST00000370765.11 | |
DST | NM_001374736.1 | c.1779-260G>T | intron_variant | ENST00000680361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.26G>T | p.Arg9Leu | missense_variant | 1/24 | 1 | NM_001723.7 | ||
DST | ENST00000680361.1 | c.1779-260G>T | intron_variant | NM_001374736.1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000480 AC: 12AN: 249974Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135122
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461752Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727168
GnomAD4 genome ? Cov.: 33
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 | Invitae | Jul 11, 2022 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 9 of the DST protein (p.Arg9Leu). This variant is present in population databases (rs201866780, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with DST-related conditions. ClinVar contains an entry for this variant (Variation ID: 541442). 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 C65"). 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