rs2230493

Variant names:

• chr3-53179641-T-C
• rs2230493
• NM_006254.4:c.180T>C
• PRKCD p.Asp60Asp

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.180T>C​(p.Asp60Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,930 control chromosomes in the GnomAD database, including 21,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1364 hom., cov: 33)
  • Exomes 𝑓: 0.16 (20035 hom.)
• Consequence: PRKCD NM_006254.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.426
• Publications: 20 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=-0.68).
• BP6: Variant 3-53179641-T-C is Benign according to our data. Variant chr3-53179641-T-C is described in ClinVar as Benign. ClinVar VariationId is 403344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.426 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 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.180T>C	p.Asp60Asp	synonymous	Exon 4 of 19	NP_006245.2
	PRKCD	NM_001354676.2		c.237T>C	p.Asp79Asp	synonymous	Exon 3 of 18	NP_001341605.1
	PRKCD	NM_001354678.2		c.228T>C	p.Asp76Asp	synonymous	Exon 3 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.180T>C	p.Asp60Asp	synonymous	Exon 4 of 19	ENSP00000331602.3	Q05655-1
	PRKCD	ENST00000394729.6	TSL:1	c.180T>C	p.Asp60Asp	synonymous	Exon 3 of 18	ENSP00000378217.2	Q05655-1
	PRKCD	ENST00000949465.1		c.180T>C	p.Asp60Asp	synonymous	Exon 3 of 18	ENSP00000619524.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18706 AN: 152136 Hom.: 1363 Cov.: 33

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.127 AC: 31911 AN: 250908 AF XY: 0.133

Gnomad AFR exome AF: 0.0605

Gnomad AMR exome AF: 0.0687

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0179

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.160 AC: 233451 AN: 1461676 Hom.: 20035 Cov.: 55 AF XY: 0.160 AC XY: 116659 AN XY: 727116

African (AFR) AF: 0.0603 AC: 2019 AN: 33478

American (AMR) AF: 0.0720 AC: 3218 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3871 AN: 26134

East Asian (EAS) AF: 0.0134 AC: 533 AN: 39700

South Asian (SAS) AF: 0.161 AC: 13892 AN: 86226

European-Finnish (FIN) AF: 0.124 AC: 6597 AN: 53410

Middle Eastern (MID) AF: 0.164 AC: 948 AN: 5764

European-Non Finnish (NFE) AF: 0.174 AC: 193503 AN: 1111868

Other (OTH) AF: 0.147 AC: 8870 AN: 60388

GnomAD4 genome AF: 0.123 AC: 18703 AN: 152254 Hom.: 1364 Cov.: 33 AF XY: 0.121 AC XY: 8985 AN XY: 74460

African (AFR) AF: 0.0631 AC: 2623 AN: 41546

American (AMR) AF: 0.101 AC: 1552 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3470

East Asian (EAS) AF: 0.0173 AC: 90 AN: 5190

South Asian (SAS) AF: 0.153 AC: 736 AN: 4822

European-Finnish (FIN) AF: 0.121 AC: 1290 AN: 10620

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11440 AN: 67990

Other (OTH) AF: 0.123 AC: 259 AN: 2108

Alfa AF: 0.149 Hom.: 2427

Bravo AF: 0.117

Asia WGS AF: 0.0750 AC: 260 AN: 3478

EpiCase AF: 0.165

EpiControl AF: 0.166

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	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	-0.68
CADD	Benign	0.27
DANN	Benign	0.35
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2230493;

hg19: chr3-53213657;

COSMIC: COSV104636409;