3-53164998-T-G

Variant names:

• chr3-53164998-T-G
• rs1483185
• NM_006254.4:c.-131-106T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006254.4(PRKCD):​c.-131-106T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,060 control chromosomes in the GnomAD database, including 46,589 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (46572 hom., cov: 31)
  • Exomes 𝑓: 0.90 (17 hom.)
• Consequence: PRKCD NM_006254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 11 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):

• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.853 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	NM_006254.4	MANE Select	c.-131-106T>G		intron	N/A	NP_006245.2
	PRKCD	NM_001316327.2		c.-131-106T>G		intron	N/A	NP_001303256.1
	PRKCD	NM_001354679.2		c.-136+3570T>G		intron	N/A	NP_001341608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.-131-106T>G		intron	N/A	ENSP00000331602.3
	PRKCD	ENST00000394729.6	TSL:1	c.-20+3570T>G		intron	N/A	ENSP00000378217.2
	PRKCD	ENST00000650739.1		c.-136+3570T>G		intron	N/A	ENSP00000498623.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117812 AN: 151900 Hom.: 46560 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.905 AC: 38 AN: 42 Hom.: 17 AF XY: 0.900 AC XY: 27 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.967 AC: 29 AN: 30

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.775 AC: 117865 AN: 152018 Hom.: 46572 Cov.: 31 AF XY: 0.779 AC XY: 57845 AN XY: 74292

African (AFR) AF: 0.612 AC: 25322 AN: 41374

American (AMR) AF: 0.783 AC: 11965 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3154 AN: 3472

East Asian (EAS) AF: 0.779 AC: 4033 AN: 5174

South Asian (SAS) AF: 0.875 AC: 4217 AN: 4818

European-Finnish (FIN) AF: 0.887 AC: 9382 AN: 10572

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57051 AN: 68016

Other (OTH) AF: 0.791 AC: 1664 AN: 2104

Alfa AF: 0.817 Hom.: 181112

Bravo AF: 0.757

Asia WGS AF: 0.801 AC: 2788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.74
PhyloP100		-0.13
PromoterAI		0.052	Neutral
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

Other links and lift over

dbSNP: rs1483185; hg19: chr3-53199014;