rs575674401
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000314191.7(PRKDC):c.3698C>T(p.Ser1233Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000255 in 1,610,456 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/19 in silico tools predict 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. S1233W) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000314191.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.3698C>T | p.Ser1233Leu | missense_variant | 31/86 | ENST00000314191.7 | NP_008835.5 | |
PRKDC | NM_001081640.2 | c.3698C>T | p.Ser1233Leu | missense_variant | 31/85 | NP_001075109.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.3698C>T | p.Ser1233Leu | missense_variant | 31/86 | 1 | NM_006904.7 | ENSP00000313420 | P1 | |
PRKDC | ENST00000338368.7 | c.3698C>T | p.Ser1233Leu | missense_variant | 31/85 | 1 | ENSP00000345182 |
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000370 AC: 9AN: 243554Hom.: 0 AF XY: 0.0000680 AC XY: 9AN XY: 132286
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1458218Hom.: 0 Cov.: 30 AF XY: 0.0000331 AC XY: 24AN XY: 724996
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2022 | The p.S1233L variant (also known as c.3698C>T), located in coding exon 31 of the PRKDC gene, results from a C to T substitution at nucleotide position 3698. The serine at codon 1233 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at