8-47785191-G-T

Variant names:

• chr8-47785191-G-T
• NM_006904.7:c.11029C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006904.7(PRKDC):​c.11029C>A​(p.Pro3677Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKDC NM_006904.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.11029C>A	p.Pro3677Thr	missense_variant	Exon 77 of 86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.11029C>A	p.Pro3677Thr	missense_variant	Exon 77 of 85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.11029C>A	p.Pro3677Thr	missense_variant	Exon 77 of 86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.11029C>A	p.Pro3677Thr	missense_variant	Exon 77 of 85	1		ENSP00000345182.4
PRKDC	ENST00000697603.1	c.3706C>A	p.Pro1236Thr	missense_variant	Exon 24 of 33			ENSP00000513358.1
PRKDC	ENST00000697602.1	n.1602C>A		non_coding_transcript_exon_variant	Exon 9 of 18

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.P3677T variant (also known as c.11029C>A), located in coding exon 77 of the PRKDC gene, results from a C to A substitution at nucleotide position 11029. The proline at codon 3677 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.27	T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	-0.024	T
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Benign	0.45	T
REVEL	Uncertain	0.39
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.39	B;.
Vest4		0.64
MutPred		0.25		Loss of catalytic residue at P3676 (P = 0.016);Loss of catalytic residue at P3676 (P = 0.016);
MVP		0.71
MPC		0.72
ClinPred		0.97	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.45
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-48697752;