Variant 1-2173988-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002744.6(PRKCZ):c.1377C>T(p.Asp459Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,612,534 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 9 hom. )

Consequence

PRKCZ
NM_002744.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.86

Variant links:

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]

PRKCZ links:

PRKCZ (HGNC:):

PRKCZ links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-2173988-C-T is Benign according to our data. Variant chr1-2173988-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388215.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.86 with no splicing effect.

BS2

High AC in GnomAd4 at 184 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	NM_002744.6 linkuse as main transcript	c.1377C>T	p.Asp459Asp	synonymous_variant	14/18	ENST00000378567.8	NP_002735.3	Q05513-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8 linkuse as main transcript	c.1377C>T	p.Asp459Asp	synonymous_variant	14/18	1	NM_002744.6	ENSP00000367830.3		Q05513-1

Frequencies

GnomAD3 genomes

AF:

0.00121

AC:

184

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00102

AC:

254

AN:

249314

Hom.:

AF XY:

0.000972

AC XY:

131

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.000206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000298

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00195

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00217

AC:

3168

AN:

1460182

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1488

AN XY:

726298

show subpopulations

Gnomad4 AFR exome

AF:

0.000689

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000466

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00268

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00121

AC:

184

AN:

152352

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00225

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00129

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00186

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

PRKCZ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.9

DANN

Benign

0.56

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over