rs3753242

Variant names:

• chr1-2138242-C-T
• rs3753242
• NM_002744.6:c.420+2895C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002744.6(PRKCZ):​c.420+2895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 152,246 control chromosomes in the GnomAD database, including 1,373 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 0.084 (1373 hom., cov: 32)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.420+2895C>T		intron_variant	Intron 5 of 17	ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8	c.420+2895C>T		intron_variant	Intron 5 of 17	1	NM_002744.6	ENSP00000367830.3

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12711 AN: 152126 Hom.: 1369 Cov.: 32

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0911

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

GnomAD4 genome AF: 0.0836 AC: 12726 AN: 152246 Hom.: 1373 Cov.: 32 AF XY: 0.0894 AC XY: 6656 AN XY: 74434

African (AFR) AF: 0.0292 AC: 1212 AN: 41554

American (AMR) AF: 0.135 AC: 2060 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3043 AN: 5166

South Asian (SAS) AF: 0.177 AC: 854 AN: 4832

European-Finnish (FIN) AF: 0.0847 AC: 898 AN: 10602

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4300 AN: 68010

Other (OTH) AF: 0.0939 AC: 198 AN: 2108

Alfa AF: 0.0799 Hom.: 3208

Bravo AF: 0.0874

Asia WGS AF: 0.342 AC: 1188 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	0.97
DANN	Benign	0.62
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3753242; hg19: chr1-2069681;