chr8-47798373-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000314191.7(PRKDC):c.10322C>T(p.Ala3441Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,607,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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. A3441A) has been classified as Likely benign.
Frequency
Consequence
ENST00000314191.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.10322C>T | p.Ala3441Val | missense_variant | 73/86 | ENST00000314191.7 | NP_008835.5 | |
PRKDC | NM_001081640.2 | c.10322C>T | p.Ala3441Val | missense_variant | 73/85 | NP_001075109.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.10322C>T | p.Ala3441Val | missense_variant | 73/86 | 1 | NM_006904.7 | ENSP00000313420 | P1 | |
PRKDC | ENST00000338368.7 | c.10322C>T | p.Ala3441Val | missense_variant | 73/85 | 1 | ENSP00000345182 | |||
PRKDC | ENST00000697603.1 | c.2999C>T | p.Ala1000Val | missense_variant | 20/33 | ENSP00000513358 | ||||
PRKDC | ENST00000697602.1 | n.895C>T | non_coding_transcript_exon_variant | 5/18 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000137 AC: 33AN: 241168Hom.: 0 AF XY: 0.000199 AC XY: 26AN XY: 130780
GnomAD4 exome AF: 0.0000749 AC: 109AN: 1455168Hom.: 0 Cov.: 30 AF XY: 0.000105 AC XY: 76AN XY: 723334
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 10, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3441 of the PRKDC protein (p.Ala3441Val). This variant is present in population databases (rs757868901, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 542002). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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