rs262654

Variant names:

• chr1-2158087-G-A
• rs262654
• NM_002744.6:c.974+1995G>A

Variant summary

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

The NM_002744.6(PRKCZ):​c.974+1995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,070 control chromosomes in the GnomAD database, including 4,627 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 0.22 (4627 hom., cov: 33)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002744.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCZ	NM_002744.6	MANE Select	c.974+1995G>A		intron	N/A	NP_002735.3
	PRKCZ	NM_001242874.3		c.662+1995G>A		intron	N/A	NP_001229803.1
	PRKCZ	NM_001350803.2		c.425+1995G>A		intron	N/A	NP_001337732.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCZ	ENST00000378567.8	TSL:1 MANE Select	c.974+1995G>A		intron	N/A	ENSP00000367830.3
	PRKCZ	ENST00000400921.6	TSL:1	c.425+1995G>A		intron	N/A	ENSP00000383712.2
	PRKCZ	ENST00000965048.1		c.974+1995G>A		intron	N/A	ENSP00000635107.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33552 AN: 151952 Hom.: 4624 Cov.: 33

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.221 AC: 33572 AN: 152070 Hom.: 4627 Cov.: 33 AF XY: 0.226 AC XY: 16759 AN XY: 74310

African (AFR) AF: 0.0503 AC: 2091 AN: 41568

American (AMR) AF: 0.327 AC: 4997 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1001 AN: 5170

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4822

European-Finnish (FIN) AF: 0.310 AC: 3265 AN: 10540

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 18990 AN: 67896

Other (OTH) AF: 0.227 AC: 479 AN: 2114

Alfa AF: 0.272 Hom.: 2693

Bravo AF: 0.215

Asia WGS AF: 0.200 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.66
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: rs262654; hg19: chr1-2089526;