3-53178367-C-T

Variant names:

• chr3-53178367-C-T
• rs2306570
• NM_006254.4:c.-19-37C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006254.4(PRKCD):​c.-19-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,468,282 control chromosomes in the GnomAD database, including 19,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1324 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17901 hom.)
• Consequence: PRKCD NM_006254.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.504
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-53178367-C-T is Benign according to our data. Variant chr3-53178367-C-T is described in ClinVar as [Benign]. Clinvar id is 1275121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCD	NM_006254.4	c.-19-37C>T		intron_variant	Intron 2 of 18	ENST00000330452.8	NP_006245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCD	ENST00000330452.8	c.-19-37C>T		intron_variant	Intron 2 of 18	1	NM_006254.4	ENSP00000331602.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18112 AN: 152174 Hom.: 1323 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.159 AC: 208695 AN: 1315988 Hom.: 17901 Cov.: 18 AF XY: 0.159 AC XY: 104630 AN XY: 657154

African (AFR) AF: 0.0458 AC: 1407 AN: 30728

American (AMR) AF: 0.0714 AC: 3005 AN: 42110

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3489 AN: 23652

East Asian (EAS) AF: 0.0135 AC: 519 AN: 38354

South Asian (SAS) AF: 0.159 AC: 12657 AN: 79656

European-Finnish (FIN) AF: 0.123 AC: 5509 AN: 44612

Middle Eastern (MID) AF: 0.160 AC: 620 AN: 3872

European-Non Finnish (NFE) AF: 0.174 AC: 173493 AN: 997870

Other (OTH) AF: 0.145 AC: 7996 AN: 55134

GnomAD4 genome AF: 0.119 AC: 18109 AN: 152294 Hom.: 1324 Cov.: 32 AF XY: 0.117 AC XY: 8702 AN XY: 74466

African (AFR) AF: 0.0496 AC: 2060 AN: 41566

American (AMR) AF: 0.0999 AC: 1529 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.0177 AC: 92 AN: 5188

South Asian (SAS) AF: 0.151 AC: 732 AN: 4832

European-Finnish (FIN) AF: 0.122 AC: 1292 AN: 10604

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

European-Non Finnish (NFE) AF: 0.168 AC: 11436 AN: 68018

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.140 Hom.: 487

Bravo AF: 0.112

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.77
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2306570; hg19: chr3-53212383;