rs908742

Positions:

• chr1-2101817-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.335-33445G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,140 control chromosomes in the GnomAD database, including 8,203 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 0.30 (8203 hom., cov: 32)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCZ	NM_002744.6	c.335-33445G>A		intron_variant		ENST00000378567.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCZ	ENST00000378567.8	c.335-33445G>A		intron_variant		1	NM_002744.6	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45811 AN: 152020 Hom.: 8201 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.301 AC: 45824 AN: 152140 Hom.: 8203 Cov.: 32 AF XY: 0.314 AC XY: 23372 AN XY: 74344

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.298

Alfa AF: 0.329 Hom.: 11514

Bravo AF: 0.286

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.032
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs908742; hg19: chr1-2033256;