Variant 3-53186199-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006254.4(PRKCD):c.1119G>A(p.Glu373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,704 control chromosomes in the GnomAD database, including 60,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6478 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53992 hom. )

Consequence

PRKCD
NM_006254.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

PRKCD (HGNC:9399): (protein kinase C delta) The protein encoded by this gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. Also, this protein can positively or negatively regulate apoptosis. Defects in this gene are a cause of autoimmune lymphoproliferative syndrome. [provided by RefSeq, Aug 2017]

PRKCD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-53186199-G-A is Benign according to our data. Variant chr3-53186199-G-A is described in ClinVar as [Benign]. Clinvar id is 403345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCD	NM_006254.4 linkuse as main transcript	c.1119G>A	p.Glu373=	synonymous_variant	13/19	ENST00000330452.8	NP_006245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCD	ENST00000330452.8 linkuse as main transcript	c.1119G>A	p.Glu373=	synonymous_variant	13/19	1	NM_006254.4	ENSP00000331602	P1	Q05655-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43862

AN:

151990

Hom.:

6470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.271

AC:

67887

AN:

250708

Hom.:

9203

AF XY:

0.271

AC XY:

36747

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.205

Gnomad SAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.270

AC:

394688

AN:

1461596

Hom.:

53992

Cov.:

AF XY:

0.271

AC XY:

196889

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.163

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.289

AC:

43906

AN:

152108

Hom.:

6478

Cov.:

AF XY:

0.287

AC XY:

21371

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.276

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.277

Hom.:

3812

Bravo

AF:

0.290

Asia WGS

AF:

0.229

AC:

796

AN:

3478

EpiCase

AF:

0.288

EpiControl

AF:

0.290

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
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

-0.54

CADD

Benign

4.4

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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