rs370182783
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000314191.7(PRKDC):āc.3574T>Cā(p.Tyr1192His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,602,470 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 ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1192C) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.3574T>C | p.Tyr1192His | missense_variant | 30/86 | ENST00000314191.7 | NP_008835.5 | |
PRKDC | NM_001081640.2 | c.3574T>C | p.Tyr1192His | missense_variant | 30/85 | NP_001075109.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.3574T>C | p.Tyr1192His | missense_variant | 30/86 | 1 | NM_006904.7 | ENSP00000313420 | P1 | |
PRKDC | ENST00000338368.7 | c.3574T>C | p.Tyr1192His | missense_variant | 30/85 | 1 | ENSP00000345182 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152268Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000414 AC: 6AN: 1450202Hom.: 0 Cov.: 30 AF XY: 0.00000556 AC XY: 4AN XY: 719212
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74400
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 19, 2022 | The p.Y1192H variant (also known as c.3574T>C), located in coding exon 30 of the PRKDC gene, results from a T to C substitution at nucleotide position 3574. The tyrosine at codon 1192 is replaced by histidine, an amino acid with similar 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. - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 20, 2018 | This sequence change replaces tyrosine with histidine at codon 1192 of the PRKDC protein (p.Tyr1192His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs370182783, ExAC 0.001%). 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: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PRKDC-related disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at