rs547696421
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006904.7(PRKDC):c.10700T>A(p.Val3567Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000312 in 1,602,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V3567V) has been classified as Likely benign.
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.10700T>A | p.Val3567Glu | missense_variant | 75/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.10700T>A | p.Val3567Glu | missense_variant | 75/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.10700T>A | p.Val3567Glu | missense_variant | 75/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.10700T>A | p.Val3567Glu | missense_variant | 75/85 | 1 | |||
PRKDC | ENST00000697603.1 | c.3377T>A | p.Val1126Glu | missense_variant | 22/33 | ||||
PRKDC | ENST00000697602.1 | n.1273T>A | non_coding_transcript_exon_variant | 7/18 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151800Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000823 AC: 2AN: 243122Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131886
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1450864Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 721216
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151908Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74220
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2018 | This sequence change replaces valine with glutamic acid at codon 3567 of the PRKDC protein (p.Val3567Glu). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glutamic acid. This variant is present in population databases (rs547696421, ExAC 0.01%). This variant has not been reported in the literature in individuals with PRKDC-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at