20-3191226-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_023935.3(DDRGK1):c.742C>T(p.Arg248Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,614,044 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R248H) has been classified as Uncertain significance.
Frequency
Consequence
NM_023935.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDRGK1 | NM_023935.3 | c.742C>T | p.Arg248Cys | missense_variant | 8/9 | ENST00000354488.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDRGK1 | ENST00000354488.8 | c.742C>T | p.Arg248Cys | missense_variant | 8/9 | 1 | NM_023935.3 | P1 | |
DDRGK1 | ENST00000496781.1 | n.359C>T | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
DDRGK1 | ENST00000470203.1 | n.181-407C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251436Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135894
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 727240
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 02, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 248 of the DDRGK1 protein (p.Arg248Cys). 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with DDRGK1-related conditions. This variant is present in population databases (rs151280429, gnomAD 0.03%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at