chr3-53182676-C-T

Variant names:

• chr3-53182676-C-T
• rs13084863
• NM_006254.4:c.572-445C>T

Variant summary

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

The NM_006254.4(PRKCD):​c.572-445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,062 control chromosomes in the GnomAD database, including 18,959 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 0.48 (18959 hom., cov: 33)
• Consequence: PRKCD NM_006254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 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.572-445C>T		intron	N/A	NP_006245.2
	PRKCD	NM_001354676.2		c.629-445C>T		intron	N/A	NP_001341605.1
	PRKCD	NM_001354678.2		c.620-445C>T		intron	N/A	NP_001341607.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.572-445C>T		intron	N/A	ENSP00000331602.3
	PRKCD	ENST00000394729.6	TSL:1	c.572-445C>T		intron	N/A	ENSP00000378217.2
	PRKCD	ENST00000697589.1		n.131C>T		non_coding_transcript_exon	Exon 1 of 12

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73284 AN: 151944 Hom.: 18938 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.482 AC: 73347 AN: 152062 Hom.: 18959 Cov.: 33 AF XY: 0.487 AC XY: 36186 AN XY: 74308

African (AFR) AF: 0.304 AC: 12619 AN: 41474

American (AMR) AF: 0.511 AC: 7813 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1816 AN: 3464

East Asian (EAS) AF: 0.852 AC: 4411 AN: 5176

South Asian (SAS) AF: 0.703 AC: 3392 AN: 4824

European-Finnish (FIN) AF: 0.526 AC: 5544 AN: 10546

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35948 AN: 67976

Other (OTH) AF: 0.512 AC: 1082 AN: 2114

Alfa AF: 0.495 Hom.: 17039

Bravo AF: 0.473

Asia WGS AF: 0.765 AC: 2657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.53
PhyloP100		-0.037
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: rs13084863; hg19: chr3-53216692;