3-53189911-C-G

Variant names:

• chr3-53189911-C-G
• rs1075865
• NM_006254.4:c.1782C>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006254.4(PRKCD):​c.1782C>G​(p.Thr594Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,614,192 control chromosomes in the GnomAD database, including 781,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (67685 hom., cov: 32)
  • Exomes 𝑓: 0.99 (713326 hom.)
• Consequence: PRKCD NM_006254.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: -0.683

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-53189911-C-G is Benign according to our data. Variant chr3-53189911-C-G is described in ClinVar as [Benign]. Clinvar id is 403347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.683 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCD	NM_006254.4	c.1782C>G	p.Thr594Thr	synonymous_variant	Exon 18 of 19	ENST00000330452.8	NP_006245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCD	ENST00000330452.8	c.1782C>G	p.Thr594Thr	synonymous_variant	Exon 18 of 19	1	NM_006254.4	ENSP00000331602.3

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142940 AN: 152190 Hom.: 67649 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.895

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.952

GnomAD3 exomes AF: 0.970 AC: 243909 AN: 251488 Hom.: 118663 AF XY: 0.969 AC XY: 131755 AN XY: 135918

Gnomad AFR exome AF: 0.802

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 0.968

Gnomad SAS exome AF: 0.894

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.987

GnomAD4 exome AF: 0.987 AC: 1443054 AN: 1461884 Hom.: 713326 Cov.: 61 AF XY: 0.985 AC XY: 716504 AN XY: 727242

Gnomad4 AFR exome AF: 0.804

Gnomad4 AMR exome AF: 0.989

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 0.976

Gnomad4 SAS exome AF: 0.900

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.978

GnomAD4 genome AF: 0.939 AC: 143032 AN: 152308 Hom.: 67685 Cov.: 32 AF XY: 0.940 AC XY: 69979 AN XY: 74472

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.953

Alfa AF: 0.950 Hom.: 17764

Bravo AF: 0.934

Asia WGS AF: 0.913 AC: 3177 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

Significance: Benign

Submissions summary: Benign:6 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2 Other:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 96. Only high quality variants are reported. -

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.23
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1075865; hg19: chr3-53223927;