Variant 1-2172067-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_002744.6(PRKCZ):c.1074C>G(p.Ala358=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,609,038 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 152 hom. )

Consequence

PRKCZ
NM_002744.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.00

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 1-2172067-C-G is Benign according to our data. Variant chr1-2172067-C-G is described in ClinVar as [Benign]. Clinvar id is 718957.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCZ	NM_002744.6 linkuse as main transcript	c.1074C>G	p.Ala358=	synonymous_variant	12/18	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.1074C>G	p.Ala358=	synonymous_variant	12/18	1	NM_002744.6	ENSP00000367830	P1	Q05513-1

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

587

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0825

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00764

AC:

1881

AN:

246284

Hom.:

AF XY:

0.00717

AC XY:

955

AN XY:

133258

show subpopulations

Gnomad AFR exome

AF:

0.000805

Gnomad AMR exome

AF:

0.000322

Gnomad ASJ exome

AF:

0.00167

Gnomad EAS exome

AF:

0.0830

Gnomad SAS exome

AF:

0.00429

Gnomad FIN exome

AF:

0.00451

Gnomad NFE exome

AF:

0.000568

Gnomad OTH exome

AF:

0.00584

GnomAD4 exome

AF:

0.00325

AC:

4732

AN:

1456704

Hom.:

152

Cov.:

AF XY:

0.00326

AC XY:

2359

AN XY:

724382

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000293

Gnomad4 ASJ exome

AF:

0.00210

Gnomad4 EAS exome

AF:

0.0821

Gnomad4 SAS exome

AF:

0.00427

Gnomad4 FIN exome

AF:

0.00431

Gnomad4 NFE exome

AF:

0.000370

Gnomad4 OTH exome

AF:

0.00641

GnomAD4 genome

AF:

0.00382

AC:

582

AN:

152334

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000793

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0817

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00405

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.028

DANN

Benign

0.45

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