chr3-53192161-G-A

Variant names:

• chr3-53192161-G-A
• rs56338517
• NM_006254.4:c.1926G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006254.4(PRKCD):​c.1926G>A​(p.Ala642Ala) 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:3
• Conservation: PhyloP100: -3.90
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal systemic lupus erythematosus type 16

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006254.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	NM_006254.4	MANE Select	c.1926G>A	p.Ala642Ala	synonymous	Exon 19 of 19	NP_006245.2
	PRKCD	NM_001354676.2		c.1983G>A	p.Ala661Ala	synonymous	Exon 18 of 18	NP_001341605.1
	PRKCD	NM_001354678.2		c.1974G>A	p.Ala658Ala	synonymous	Exon 18 of 18	NP_001341607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.1926G>A	p.Ala642Ala	synonymous	Exon 19 of 19	ENSP00000331602.3	Q05655-1
	PRKCD	ENST00000394729.6	TSL:1	c.1926G>A	p.Ala642Ala	synonymous	Exon 18 of 18	ENSP00000378217.2	Q05655-1
	PRKCD	ENST00000949465.1		c.1962G>A	p.Ala654Ala	synonymous	Exon 18 of 18	ENSP00000619524.1

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

GnomAD2 exomes AF: 0.00768 AC: 1930 AN: 251464 AF XY: 0.00571

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 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

African (AFR) AF: 0.104 AC: 3471 AN: 33474

American (AMR) AF: 0.00754 AC: 337 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00537 AC: 31 AN: 5768

European-Non Finnish (NFE) AF: 0.000328 AC: 365 AN: 1111998

Other (OTH) AF: 0.00742 AC: 448 AN: 60396

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

African (AFR) AF: 0.0971 AC: 4024 AN: 41458

American (AMR) AF: 0.0126 AC: 192 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68004

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.0145 Hom.: 77

Bravo AF: 0.0338

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.20
DANN	Benign	0.63
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56338517; hg19: chr3-53226177;