8-47774197-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006904.7(PRKDC):āc.12363G>Cā(p.Trp4121Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,504 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W4121S) has been classified as Uncertain significance.
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.12363G>C | p.Trp4121Cys | missense_variant | 86/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.12270G>C | p.Trp4090Cys | missense_variant | 85/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.12363G>C | p.Trp4121Cys | missense_variant | 86/86 | 1 | NM_006904.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432504Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 709710
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2021 | The p.W4121C variant (also known as c.12363G>C), located in coding exon 86 of the PRKDC gene, results from a G to C substitution at nucleotide position 12363. The tryptophan at codon 4121 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.