rs262654

Positions:

• chr1-2158087-G-A

Variant summary

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

The NM_002744.6(PRKCZ):​c.974+1995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,070 control chromosomes in the GnomAD database, including 4,627 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 0.22 (4627 hom., cov: 33)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.974+1995G>A		intron_variant		ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8	c.974+1995G>A		intron_variant		1	NM_002744.6	ENSP00000367830	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33552 AN: 151952 Hom.: 4624 Cov.: 33

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33572 AN: 152070 Hom.: 4627 Cov.: 33 AF XY: 0.226 AC XY: 16759 AN XY: 74310

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.227

Alfa AF: 0.272 Hom.: 2693

Bravo AF: 0.215

Asia WGS AF: 0.200 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs262654; hg19: chr1-2089526;