rs606231296

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP2PP3_StrongPP5

The ENST00000330452.8(PRKCD):​c.1528G>A​(p.Gly510Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRKCD
ENST00000330452.8 missense

Scores

12
6
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 10.0
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PRKCD. . Gene score misZ 3.1145 (greater than the threshold 3.09). Trascript score misZ 3.8606 (greater than threshold 3.09). GenCC has associacion of gene with common variable immunodeficiency, autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD, autoimmune lymphoproliferative syndrome, autosomal systemic lupus erythematosus type 16.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.99
PP5
Variant 3-53188832-G-A is Pathogenic according to our data. Variant chr3-53188832-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 157674.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRKCDNM_006254.4 linkuse as main transcriptc.1528G>A p.Gly510Ser missense_variant 16/19 ENST00000330452.8 NP_006245.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRKCDENST00000330452.8 linkuse as main transcriptc.1528G>A p.Gly510Ser missense_variant 16/191 NM_006254.4 ENSP00000331602 P1Q05655-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251184
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135822
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461836
Hom.:
0
Cov.:
43
AF XY:
0.00
AC XY:
0
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 01, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T;T
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
.;D
M_CAP
Pathogenic
0.64
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Uncertain
0.68
D
MutationAssessor
Pathogenic
3.0
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Pathogenic
0.80
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.97
MutPred
0.94
Gain of glycosylation at T507 (P = 0.011);Gain of glycosylation at T507 (P = 0.011);
MVP
0.96
MPC
1.9
ClinPred
1.0
D
GERP RS
6.1
Varity_R
0.98
gMVP
0.97

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs606231296; hg19: chr3-53222848; API