chr20-3190805-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_023935.3(DDRGK1):c.793C>T(p.Arg265Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R265R) has been classified as Likely benign.
Frequency
Consequence
NM_023935.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDRGK1 | NM_023935.3 | c.793C>T | p.Arg265Trp | missense_variant | 9/9 | ENST00000354488.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDRGK1 | ENST00000354488.8 | c.793C>T | p.Arg265Trp | missense_variant | 9/9 | 1 | NM_023935.3 | P1 | |
DDRGK1 | ENST00000496781.1 | n.410C>T | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
DDRGK1 | ENST00000470203.1 | n.195C>T | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245616Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 132918
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460126Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6AN XY: 726262
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2023 | The c.793C>T (p.R265W) alteration is located in exon 9 (coding exon 9) of the DDRGK1 gene. This alteration results from a C to T substitution at nucleotide position 793, causing the arginine (R) at amino acid position 265 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 265 of the DDRGK1 protein (p.Arg265Trp). This variant is present in population databases (rs781609753, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DDRGK1-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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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