rs369745616
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001723.7(DST):c.5911G>C(p.Asp1971His) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D1971G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001723.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.5911G>C | p.Asp1971His | missense_variant | 23/24 | ENST00000370765.11 | |
DST | NM_001374736.1 | c.4930-3639G>C | intron_variant | ENST00000680361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.5911G>C | p.Asp1971His | missense_variant | 23/24 | 1 | NM_001723.7 | ||
DST | ENST00000680361.1 | c.4930-3639G>C | intron_variant | NM_001374736.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251198Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135750
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461854Hom.: 0 Cov.: 36 AF XY: 0.00000825 AC XY: 6AN XY: 727230
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
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 | Nov 22, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 566950). This variant has not been reported in the literature in individuals affected with DST-related conditions. This variant is present in population databases (rs369745616, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1971 of the DST protein (p.Asp1971His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at