rs56123237
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006904.7(PRKDC):c.12138C>T(p.Tyr4046=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,613,806 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 3 hom. )
Consequence
PRKDC
NM_006904.7 synonymous
NM_006904.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.306
Genes affected
PRKDC (HGNC:9413): (protein kinase, DNA-activated, catalytic subunit) This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 8-47776888-G-A is Benign according to our data. Variant chr8-47776888-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.306 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.12138C>T | p.Tyr4046= | synonymous_variant | 85/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.12045C>T | p.Tyr4015= | synonymous_variant | 84/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.12138C>T | p.Tyr4046= | synonymous_variant | 85/86 | 1 | NM_006904.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00188 AC: 286AN: 152078Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00112 AC: 278AN: 249100Hom.: 1 AF XY: 0.00116 AC XY: 157AN XY: 135162
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GnomAD4 exome AF: 0.00134 AC: 1962AN: 1461610Hom.: 3 Cov.: 31 AF XY: 0.00132 AC XY: 959AN XY: 727080
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GnomAD4 genome ? AF: 0.00188 AC: 286AN: 152196Hom.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132AN XY: 74422
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | PRKDC: BP4, BP7 - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at