rs3128309

Positions:

• chr1-2174439-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.1406-315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 152,336 control chromosomes in the GnomAD database, including 531 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 0.077 (531 hom., cov: 33)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCZ	NM_002744.6	c.1406-315G>A		intron_variant		ENST00000378567.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCZ	ENST00000378567.8	c.1406-315G>A		intron_variant		1	NM_002744.6	P1

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11659 AN: 152218 Hom.: 531 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0766 AC: 11665 AN: 152336 Hom.: 531 Cov.: 33 AF XY: 0.0727 AC XY: 5412 AN XY: 74494

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.0542

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.0697

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0591

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0780 Hom.: 105

Bravo AF: 0.0736

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3128309; hg19: chr1-2105878;