rs8178208

Variant names:

• chr8-47817561-C-A
• NM_006904.7:c.9446G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-47817561-C-A
• chr8-47817561-C-G
• chr8-47817561-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006904.7(PRKDC):​c.9446G>T​(p.Gly3149Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3149D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKDC NM_006904.7 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.9446G>T	p.Gly3149Val	missense_variant, splice_region_variant	Exon 68 of 86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.9446G>T	p.Gly3149Val	missense_variant, splice_region_variant	Exon 68 of 85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.9446G>T	p.Gly3149Val	missense_variant, splice_region_variant	Exon 68 of 86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.9446G>T	p.Gly3149Val	missense_variant, splice_region_variant	Exon 68 of 85	1		ENSP00000345182.4
PRKDC	ENST00000697603.1	c.2123G>T	p.Gly708Val	missense_variant, splice_region_variant	Exon 15 of 33			ENSP00000513358.1
PRKDC	ENST00000697607.1	n.978G>T		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.41	T
REVEL	Benign	0.25
Sift4G	Benign	0.41	T;T
Polyphen		0.93	P;.
Vest4		0.31
MutPred		0.55		Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);
MVP		0.63
MPC		0.71
ClinPred		0.82	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.72		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.72		Position offset: -18

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: chr8-48730122;