rs2306574

Variant names:

• chr3-53188745-C-T
• rs2306574
• NM_006254.4:c.1441C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-53188745-C-T
• chr3-53188745-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006254.4(PRKCD):​c.1441C>T​(p.Leu481Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,613,980 control chromosomes in the GnomAD database, including 482,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43178 hom., cov: 32)
  • Exomes 𝑓: 0.77 (439812 hom.)
• Consequence: PRKCD NM_006254.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: 3.40
• Publications: 31 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 3-53188745-C-T is Benign according to our data. Variant chr3-53188745-C-T is described in ClinVar as Benign. ClinVar VariationId is 403346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 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.1441C>T	p.Leu481Leu	synonymous	Exon 16 of 19	NP_006245.2
	PRKCD	NM_001354676.2		c.1498C>T	p.Leu500Leu	synonymous	Exon 15 of 18	NP_001341605.1
	PRKCD	NM_001354678.2		c.1489C>T	p.Leu497Leu	synonymous	Exon 15 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.1441C>T	p.Leu481Leu	synonymous	Exon 16 of 19	ENSP00000331602.3	Q05655-1
	PRKCD	ENST00000394729.6	TSL:1	c.1441C>T	p.Leu481Leu	synonymous	Exon 15 of 18	ENSP00000378217.2	Q05655-1
	PRKCD	ENST00000949465.1		c.1477C>T	p.Leu493Leu	synonymous	Exon 15 of 18	ENSP00000619524.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114391 AN: 152020 Hom.: 43143 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.737

GnomAD2 exomes AF: 0.752 AC: 188986 AN: 251426 AF XY: 0.746

Gnomad AFR exome AF: 0.722

Gnomad AMR exome AF: 0.765

Gnomad ASJ exome AF: 0.770

Gnomad EAS exome AF: 0.787

Gnomad FIN exome AF: 0.741

Gnomad NFE exome AF: 0.772

Gnomad OTH exome AF: 0.757

GnomAD4 exome AF: 0.775 AC: 1132236 AN: 1461840 Hom.: 439812 Cov.: 70 AF XY: 0.771 AC XY: 560333 AN XY: 727218

African (AFR) AF: 0.723 AC: 24203 AN: 33476

American (AMR) AF: 0.760 AC: 33983 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 20072 AN: 26136

East Asian (EAS) AF: 0.830 AC: 32950 AN: 39698

South Asian (SAS) AF: 0.665 AC: 57366 AN: 86258

European-Finnish (FIN) AF: 0.743 AC: 39710 AN: 53412

Middle Eastern (MID) AF: 0.701 AC: 4041 AN: 5768

European-Non Finnish (NFE) AF: 0.786 AC: 873478 AN: 1111980

Other (OTH) AF: 0.769 AC: 46433 AN: 60390

GnomAD4 genome AF: 0.752 AC: 114483 AN: 152140 Hom.: 43178 Cov.: 32 AF XY: 0.750 AC XY: 55754 AN XY: 74376

African (AFR) AF: 0.719 AC: 29853 AN: 41504

American (AMR) AF: 0.739 AC: 11299 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4069 AN: 5170

South Asian (SAS) AF: 0.665 AC: 3209 AN: 4824

European-Finnish (FIN) AF: 0.744 AC: 7865 AN: 10578

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53073 AN: 67978

Other (OTH) AF: 0.738 AC: 1560 AN: 2114

Alfa AF: 0.768 Hom.: 26457

Bravo AF: 0.756

Asia WGS AF: 0.736 AC: 2561 AN: 3476

EpiCase AF: 0.764

EpiControl AF: 0.760

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (2)
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		3.4
Mutation Taster		=70/30	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

Other links and lift over

dbSNP: rs2306574; hg19: chr3-53222761; COSMIC: COSV57846443; COSMIC: COSV57846443;