rs385039

Positions:

• chr1-2145970-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.553-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,461,188 control chromosomes in the GnomAD database, including 55,510 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 0.24 (4876 hom., cov: 32)
  • Exomes 𝑓: 0.27 (50634 hom.)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	NM_002744.6	c.553-57A>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.553-57A>G		intron_variant		1	NM_002744.6	ENSP00000367830.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35854 AN: 152070 Hom.: 4873 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.274 AC: 358766 AN: 1309000 Hom.: 50634 AF XY: 0.275 AC XY: 181065 AN XY: 658572

Gnomad4 AFR exome AF: 0.0969

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.236 AC: 35878 AN: 152188 Hom.: 4876 Cov.: 32 AF XY: 0.240 AC XY: 17871 AN XY: 74408

Gnomad4 AFR AF: 0.0998

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.240

Alfa AF: 0.268 Hom.: 1246

Bravo AF: 0.231

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs385039; hg19: chr1-2077409; COSMIC: COSV66065809; COSMIC: COSV66065809;