chr1-205169234-T-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015375.3(DSTYK):c.1253A>C(p.Asp418Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D418G) has been classified as Uncertain significance.
Frequency
Consequence
NM_015375.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSTYK | NM_015375.3 | c.1253A>C | p.Asp418Ala | missense_variant | 3/13 | ENST00000367162.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSTYK | ENST00000367162.8 | c.1253A>C | p.Asp418Ala | missense_variant | 3/13 | 1 | NM_015375.3 | P1 | |
DSTYK | ENST00000367161.7 | c.1253A>C | p.Asp418Ala | missense_variant | 3/12 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251298Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135810
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461766Hom.: 0 Cov.: 32 AF XY: 0.0000605 AC XY: 44AN XY: 727192
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74460
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals affected with DSTYK-related conditions. This variant is present in population databases (rs555607162, ExAC 0.05%). This sequence change replaces aspartic acid with alanine at codon 418 of the DSTYK protein (p.Asp418Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at