1-2111641-T-G

Position:

• chr1-2111641-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002744.6(PRKCZ):​c.335-23621T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,132 control chromosomes in the GnomAD database, including 5,310 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 0.26 (5305 hom., cov: 32)
  • Exomes 𝑓: 0.22 (5 hom.)
• Consequence: PRKCZ NM_002744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCZ	NM_002744.6	c.335-23621T>G		intron_variant		ENST00000378567.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCZ	ENST00000378567.8	c.335-23621T>G		intron_variant		1	NM_002744.6	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39412 AN: 151898 Hom.: 5294 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.216 AC: 25 AN: 116 Hom.: 5 Cov.: 0 AF XY: 0.239 AC XY: 21 AN XY: 88

Gnomad4 AFR exome AF: 0.333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.259 AC: 39445 AN: 152016 Hom.: 5305 Cov.: 32 AF XY: 0.263 AC XY: 19545 AN XY: 74310

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.267

Alfa AF: 0.266 Hom.: 3052

Bravo AF: 0.262

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6603813; hg19: chr1-2043080;