rs451061

Positions:

• chr1-2143629-G-C
• chr1-2143629-G-T

Variant summary

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

The NM_002744.6(PRKCZ):​c.421-581G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,132 control chromosomes in the GnomAD database, including 11,641 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 0.39 (11640 hom., cov: 33)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.421-581G>C		intron_variant		ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8	c.421-581G>C		intron_variant		1	NM_002744.6	ENSP00000367830	P1
	ENST00000606533.1	n.1651C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59266 AN: 151992 Hom.: 11614 Cov.: 33

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.364 AC: 8 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.390 AC: 59355 AN: 152110 Hom.: 11640 Cov.: 33 AF XY: 0.388 AC XY: 28853 AN XY: 74342

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.387

Alfa AF: 0.250 Hom.: 555

Bravo AF: 0.393

Asia WGS AF: 0.332 AC: 1155 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	0.28
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs451061; hg19: chr1-2075068; COSMIC: COSV66071725; COSMIC: COSV66071725;