rs376587897
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001723.7(DST):c.4123A>G(p.Asn1375Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.4123A>G | p.Asn1375Asp | missense_variant | 23/24 | ENST00000370765.11 | |
DST | NM_001374736.1 | c.4929+4619A>G | intron_variant | ENST00000680361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.4123A>G | p.Asn1375Asp | missense_variant | 23/24 | 1 | NM_001723.7 | ||
DST | ENST00000680361.1 | c.4929+4619A>G | intron_variant | NM_001374736.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251200Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135772
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461882Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 727244
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
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 | Apr 23, 2022 | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1375 of the DST protein (p.Asn1375Asp). This variant is present in population databases (rs376587897, gnomAD 0.01%). 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: 541447). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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