dbSNP rs55709737: PRKCD:p.Cys247Cys (chr3-53183535-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006254.4(PRKCD):c.741C>T(p.Cys247Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,614,216 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 11 hom. )

Consequence

PRKCD
NM_006254.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.10

Publications

2 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):

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

PRKCD links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006254.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 3-53183535-C-T is Benign according to our data. Variant chr3-53183535-C-T is described in ClinVar as Benign. ClinVar VariationId is 474770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.1 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00692 (1054/152356) while in subpopulation AFR AF = 0.0243 (1009/41572). AF 95% confidence interval is 0.023. There are 13 homozygotes in GnomAd4. There are 500 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR,AD gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRKCD	NM_006254.4	MANE Select	c.741C>T	p.Cys247Cys	synonymous	Exon 9 of 19	NP_006245.2
PRKCD	NM_001354676.2		c.798C>T	p.Cys266Cys	synonymous	Exon 8 of 18	NP_001341605.1
PRKCD	NM_001354678.2		c.789C>T	p.Cys263Cys	synonymous	Exon 8 of 18	NP_001341607.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKCD	ENST00000330452.8	TSL:1 MANE Select	c.741C>T	p.Cys247Cys	synonymous	Exon 9 of 19	ENSP00000331602.3	Q05655-1
PRKCD	ENST00000394729.6	TSL:1	c.741C>T	p.Cys247Cys	synonymous	Exon 8 of 18	ENSP00000378217.2	Q05655-1
PRKCD	ENST00000949465.1		c.777C>T	p.Cys259Cys	synonymous	Exon 8 of 18	ENSP00000619524.1

Frequencies

GnomAD3 genomes

AF:

0.00691

AC:

1052

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00174

AC:

438

AN:

251404

AF XY:

0.00112

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000605

AC:

885

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0222

AC:

742

AN:

33480

American (AMR)

AF:

0.000783

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111988

Other (OTH)

AF:

0.00137

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00692

AC:

1054

AN:

152356

Hom.:

Cov.:

AF XY:

0.00671

AC XY:

500

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0243

AC:

1009

AN:

41572

American (AMR)

AF:

0.00202

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

166

222

277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00362

Hom.:

Bravo

AF:

0.00766

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

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 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.2

(source)

DANN

Benign

0.58

PhyloP100

-1.1

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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

Computational scores

Splicing

Publications

Other links and lift over