rs2503706

Positions:

• chr1-2143812-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002744.6(PRKCZ):​c.421-398A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 161,426 control chromosomes in the GnomAD database, including 48,488 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (46088 hom., cov: 33)
  • Exomes 𝑓: 0.71 (2400 hom.)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02

Genes affected

PRKCZ (HGNC:9412): (protein kinase C zeta) Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCZ	NM_002744.6	c.421-398A>G		intron_variant		ENST00000378567.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCZ	ENST00000378567.8	c.421-398A>G		intron_variant		1	NM_002744.6	P1
	ENST00000606533.1	n.1468T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116922 AN: 152096 Hom.: 46016 Cov.: 33

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.714 AC: 6581 AN: 9212 Hom.: 2400 Cov.: 0 AF XY: 0.707 AC XY: 3328 AN XY: 4706

Gnomad4 AFR exome AF: 0.935

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.620

Gnomad4 EAS exome AF: 0.960

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 0.658

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.725

GnomAD4 genome AF: 0.769 AC: 117055 AN: 152214 Hom.: 46088 Cov.: 33 AF XY: 0.771 AC XY: 57385 AN XY: 74414

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.757

Alfa AF: 0.735 Hom.: 6113

Bravo AF: 0.784

Asia WGS AF: 0.882 AC: 3064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.22

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2503706; hg19: chr1-2075251;