Variant chr1-2150781-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002744.6(PRKCZ):c.688-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,608,516 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 7 hom. )

Consequence

PRKCZ
NM_002744.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001917

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.397

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-2150781-C-T is Benign according to our data. Variant chr1-2150781-C-T is described in ClinVar as [Benign]. Clinvar id is 718387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00538 (819/152312) while in subpopulation AFR AF= 0.0169 (704/41568). AF 95% confidence interval is 0.0159. There are 10 homozygotes in gnomad4. There are 405 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 819 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	NM_002744.6 linkuse as main transcript	c.688-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8 linkuse as main transcript	c.688-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002744.6	ENSP00000367830	P1	Q05513-1

Frequencies

GnomAD3 genomes

AF:

0.00538

AC:

819

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00170

AC:

424

AN:

248812

Hom.:

AF XY:

0.00134

AC XY:

180

AN XY:

134658

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.000304

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000489

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000973

AC:

1417

AN:

1456204

Hom.:

Cov.:

AF XY:

0.000895

AC XY:

648

AN XY:

723742

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.000270

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.00178

GnomAD4 genome

AF:

0.00538

AC:

819

AN:

152312

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.00398

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.00637

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.57

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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