1-2140117-A-G

Position:

• chr1-2140117-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.421-4093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,172 control chromosomes in the GnomAD database, including 44,497 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 0.76 (44497 hom., cov: 33)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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 (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.421-4093A>G		intron_variant		ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8	c.421-4093A>G		intron_variant		1	NM_002744.6	ENSP00000367830	P1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115570 AN: 152054 Hom.: 44461 Cov.: 33

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.760 AC: 115661 AN: 152172 Hom.: 44497 Cov.: 33 AF XY: 0.756 AC XY: 56234 AN XY: 74378

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.757

Alfa AF: 0.728 Hom.: 5075

Bravo AF: 0.764

Asia WGS AF: 0.797 AC: 2773 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	1.4
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs436045; hg19: chr1-2071556;