rs1038089558
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):āc.1676G>Cā(p.Ser559Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000345 in 1,567,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.1676G>C | p.Ser559Thr | missense_variant | 16/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.1676G>C | p.Ser559Thr | missense_variant | 16/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.1676G>C | p.Ser559Thr | missense_variant | 16/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.1676G>C | p.Ser559Thr | missense_variant | 16/85 | 1 | |||
PRKDC | ENST00000697591.1 | n.2509G>C | non_coding_transcript_exon_variant | 15/15 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000105 AC: 2AN: 190160Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 101828
GnomAD4 exome AF: 0.0000360 AC: 51AN: 1415150Hom.: 0 Cov.: 29 AF XY: 0.0000300 AC XY: 21AN XY: 700500
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2023 | The c.1676G>C (p.S559T) alteration is located in exon 16 (coding exon 16) of the PRKDC gene. This alteration results from a G to C substitution at nucleotide position 1676, causing the serine (S) at amino acid position 559 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, 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 | Invitae | Jun 20, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRKDC protein function. ClinVar contains an entry for this variant (Variation ID: 542008). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 559 of the PRKDC protein (p.Ser559Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at