rs757396169
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):āc.1003A>Gā(p.Lys335Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000249 in 1,607,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign 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. K335Q) has been classified as Uncertain significance.
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.1003A>G | p.Lys335Glu | missense_variant | 11/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.1003A>G | p.Lys335Glu | missense_variant | 11/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.1003A>G | p.Lys335Glu | missense_variant | 11/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.1003A>G | p.Lys335Glu | missense_variant | 11/85 | 1 | |||
PRKDC | ENST00000535375.1 | n.290A>G | non_coding_transcript_exon_variant | 1/2 | 3 | ||||
PRKDC | ENST00000697591.1 | n.1044A>G | non_coding_transcript_exon_variant | 11/15 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000414 AC: 10AN: 241668Hom.: 0 AF XY: 0.0000535 AC XY: 7AN XY: 130898
GnomAD4 exome AF: 0.0000261 AC: 38AN: 1455304Hom.: 0 Cov.: 30 AF XY: 0.0000194 AC XY: 14AN XY: 723438
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74390
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 31, 2021 | The p.K335E variant (also known as c.1003A>G), located in coding exon 11 of the PRKDC gene, results from an A to G substitution at nucleotide position 1003. The lysine at codon 335 is replaced by glutamic acid, an amino acid with similar 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at