Variant 3-170275238-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002740.6(PRKCI):c.656A>G(p.Tyr219Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000177 in 1,570,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

PRKCI
NM_002740.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

PRKCI (HGNC:9404): (protein kinase C iota) This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X. [provided by RefSeq, Jul 2008]

PRKCI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRKCI	NM_002740.6 linkuse as main transcript	c.656A>G	p.Tyr219Cys	missense_variant	8/18	ENST00000295797.5
PRKCI	XM_047448575.1 linkuse as main transcript	c.314A>G	p.Tyr105Cys	missense_variant	7/17
PRKCI	XM_047448574.1 linkuse as main transcript	c.656A>G	p.Tyr219Cys	missense_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCI	ENST00000295797.5 linkuse as main transcript	c.656A>G	p.Tyr219Cys	missense_variant	8/18	1	NM_002740.6	P1

Frequencies

GnomAD3 genomes

AF:

0.000147

AC:

AN:

142662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000776

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000217

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000211

Gnomad OTH

AF:

0.000516

GnomAD3 exomes

AF:

0.000139

AC:

AN:

229712

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

124634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000779

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000233

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000180

AC:

257

AN:

1428156

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

135

AN XY:

709598

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000102

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000154

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000209

Gnomad4 OTH exome

AF:

0.000170

GnomAD4 genome

AF:

0.000147

AC:

AN:

142748

Hom.:

Cov.:

AF XY:

0.0000876

AC XY:

AN XY:

68484

show subpopulations

Gnomad4 AFR

AF:

0.0000774

Gnomad4 AMR

AF:

0.000146

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000217

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000211

Gnomad4 OTH

AF:

0.000510

Alfa

AF:

0.000249

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000124

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.656A>G (p.Y219C) alteration is located in exon 8 (coding exon 8) of the PRKCI gene. This alteration results from a A to G substitution at nucleotide position 656, causing the tyrosine (Y) at amino acid position 219 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.092

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

REVEL

Benign

0.24

Sift

Benign

0.17

Sift4G

Benign

0.18

Polyphen

0.0010

Vest4

0.84

MVP

0.85

MPC

1.1

ClinPred

0.093

GERP RS

5.2

Varity_R

0.13

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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