Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001354676.2(PRKCD):c.1317+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,848 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 13 hom. )

Consequence

PRKCD
NM_001354676.2 splice_region, intron

Scores

Splicing: ADA: 0.0002248

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.647

Publications

0 publications found

Variant links:

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

PRKCD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-53186346-C-T is Benign according to our data. Variant chr3-53186346-C-T is described in ClinVar as Benign. ClinVar VariationId is 474765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00252 (383/152282) while in subpopulation EAS AF = 0.00193 (10/5182). AF 95% confidence interval is 0.00148. There are 4 homozygotes in GnomAd4. There are 245 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354676.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PRKCD	NM_006254.4	MANE Select	c.1260+6C>T	splice_region intron	N/A	NP_006245.2
PRKCD	NM_001354676.2		c.1317+6C>T	splice_region intron	N/A	NP_001341605.1
PRKCD	NM_001354678.2		c.1308+6C>T	splice_region intron	N/A	NP_001341607.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.1260+6C>T	splice_region intron	N/A	ENSP00000331602.3
PRKCD	ENST00000394729.6	TSL:1	c.1260+6C>T	splice_region intron	N/A	ENSP00000378217.2
PRKCD	ENST00000949465.1		c.1296+6C>T	splice_region intron	N/A	ENSP00000619524.1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0196

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00271

AC:

677

AN:

249866

AF XY:

0.00258

show subpopulations

Gnomad AFR exome

AF:

0.00204

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.0200

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00129

AC:

1889

AN:

1461566

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

966

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

33474

American (AMR)

AF:

0.000403

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26108

East Asian (EAS)

AF:

0.00176

AC:

AN:

39700

South Asian (SAS)

AF:

0.000139

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.0204

AC:

1087

AN:

53328

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000510

AC:

567

AN:

1111858

Other (OTH)

AF:

0.00134

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00252

AC:

383

AN:

152282

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

245

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00181

AC:

AN:

41546

American (AMR)

AF:

0.000523

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0196

AC:

208

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00110

AC:

AN:

68012

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00122

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (2)

not provided (1)

PRKCD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.67

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.026

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over