rs3795277

Positions:

• chr1-2049679-A-C

Variant summary

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

The XM_047425255.1(PRKCZ):​c.56+1004A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,458 control chromosomes in the GnomAD database, including 699 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 0.083 (697 hom., cov: 33)
  • Exomes 𝑓: 0.084 (2 hom.)
• Consequence: PRKCZ XM_047425255.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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]

PRKCZ-DT (HGNC:55824): (PRKCZ divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	XM_047425255.1	c.56+1004A>C		intron_variant			XP_047281211.1
PRKCZ-DT	NR_135509.1	n.204-13T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCZ-DT	ENST00000449154.1	n.204-13T>G		intron_variant		3
PRKCZ-DT	ENST00000445600.1	n.-28T>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12596 AN: 152018 Hom.: 694 Cov.: 33

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0825

GnomAD4 exome AF: 0.0839 AC: 27 AN: 322 Hom.: 2 Cov.: 0 AF XY: 0.0796 AC XY: 18 AN XY: 226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0829 AC: 12608 AN: 152136 Hom.: 697 Cov.: 33 AF XY: 0.0868 AC XY: 6457 AN XY: 74372

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.0885

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.0854

Alfa AF: 0.0836 Hom.: 474

Bravo AF: 0.0803

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3795277; hg19: chr1-1981118;