chr3-53189986-T-C

Variant names:

• chr3-53189986-T-C
• rs900495
• NM_006254.4:c.1857T>C

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.1857T>C​(p.Pro619Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,614,182 control chromosomes in the GnomAD database, including 792,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68823 hom., cov: 33)
  • Exomes 𝑓: 0.99 (723514 hom.)
• Consequence: PRKCD NM_006254.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: -0.675
• Publications: 19 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=-0.66).
• BP6: Variant 3-53189986-T-C is Benign according to our data. Variant chr3-53189986-T-C is described in ClinVar as Benign. ClinVar VariationId is 403348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.675 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.1857T>C	p.Pro619Pro	synonymous	Exon 18 of 19	NP_006245.2
	PRKCD	NM_001354676.2		c.1914T>C	p.Pro638Pro	synonymous	Exon 17 of 18	NP_001341605.1
	PRKCD	NM_001354678.2		c.1905T>C	p.Pro635Pro	synonymous	Exon 17 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.1857T>C	p.Pro619Pro	synonymous	Exon 18 of 19	ENSP00000331602.3	Q05655-1
	PRKCD	ENST00000394729.6	TSL:1	c.1857T>C	p.Pro619Pro	synonymous	Exon 17 of 18	ENSP00000378217.2	Q05655-1
	PRKCD	ENST00000949465.1		c.1893T>C	p.Pro631Pro	synonymous	Exon 17 of 18	ENSP00000619524.1

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144237 AN: 152206 Hom.: 68786 Cov.: 33

Gnomad AFR AF: 0.819

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.958

GnomAD2 exomes AF: 0.987 AC: 248047 AN: 251438 AF XY: 0.990

Gnomad AFR exome AF: 0.818

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.995 AC: 1453869 AN: 1461858 Hom.: 723514 Cov.: 70 AF XY: 0.995 AC XY: 723819 AN XY: 727232

African (AFR) AF: 0.819 AC: 27407 AN: 33480

American (AMR) AF: 0.990 AC: 44281 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 26109 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39699 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86220 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53394 AN: 53394

Middle Eastern (MID) AF: 0.990 AC: 5709 AN: 5768

European-Non Finnish (NFE) AF: 0.999 AC: 1111395 AN: 1112006

Other (OTH) AF: 0.988 AC: 59655 AN: 60394

GnomAD4 genome AF: 0.948 AC: 144331 AN: 152324 Hom.: 68823 Cov.: 33 AF XY: 0.950 AC XY: 70749 AN XY: 74486

African (AFR) AF: 0.819 AC: 34039 AN: 41550

American (AMR) AF: 0.979 AC: 14987 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3469 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67970 AN: 68034

Other (OTH) AF: 0.959 AC: 2023 AN: 2110

Alfa AF: 0.979 Hom.: 88879

Bravo AF: 0.940

Asia WGS AF: 0.987 AC: 3434 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		-0.68
Mutation Taster		=93/7	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: rs900495; hg19: chr3-53224002; COSMIC: COSV108148447;