rs56338517

chr3-53192161-G-A

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.1926G>A(p.Ala642=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,613,984 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (205 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (204 hom.)
• Consequence: PRKCD NM_006254.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.90

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=-0.71).
• BP6: Variant 3-53192161-G-A is Benign according to our data. Variant chr3-53192161-G-A is described in ClinVar as [Benign]. Clinvar id is 474767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCD	NM_006254.4	c.1926G>A	p.Ala642=	synonymous_variant	19/19	ENST00000330452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCD	ENST00000330452.8	c.1926G>A	p.Ala642=	synonymous_variant	19/19	1	NM_006254.4	P1

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4307 AN: 151992 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.00768 AC: 1930 AN: 251464 Hom.: 80 AF XY: 0.00571 AC XY: 776 AN XY: 135916

Gnomad AFR exome AF: 0.0990

Gnomad AMR exome AF: 0.00645

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000571

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00320 AC: 4679 AN: 1461872 Hom.: 204 Cov.: 31 AF XY: 0.00285 AC XY: 2074 AN XY: 727240

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00754

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000328

Gnomad4 OTH exome AF: 0.00742

GnomAD4 genome AF: 0.0283 AC: 4309 AN: 152112 Hom.: 205 Cov.: 32 AF XY: 0.0274 AC XY: 2035 AN XY: 74350

Gnomad4 AFR AF: 0.0971

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0157 Hom.: 53

Bravo AF: 0.0338

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.20
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs56338517; hg19: chr3-53226177;