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GeneBe

rs55709737

chr3-53183535-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_006254.4(PRKCD):c.741C>T(p.Cys247=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-53183535-C-T is Benign according to our data. Variant chr3-53183535-C-T is described in ClinVar as [Benign]. Clinvar id is 474770.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.1 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCDNM_006254.4 linkuse as main transcriptc.741C>T p.Cys247= synonymous_variant 9/19 ENST00000330452.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCDENST00000330452.8 linkuse as main transcriptc.741C>T p.Cys247= synonymous_variant 9/191 NM_006254.4 P1Q05655-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00691
AC:
1052
AN:
152238
Hom.:
13
Cov.:
33
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
GnomAD3 exomes
AF:
0.00174
AC:
438
AN:
251404
Hom.:
4
AF XY:
0.00112
AC XY:
152
AN XY:
135878
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 SAS 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.:
11
Cov.:
32
AF XY:
0.000494
AC XY:
359
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0222
Gnomad4 AMR exome
AF:
0.000783
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.00137
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00692
AC:
1054
AN:
152356
Hom.:
13
Cov.:
33
AF XY:
0.00671
AC XY:
500
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0243
Gnomad4 AMR
AF:
0.00202
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00342
Hom.:
1
Bravo
AF:
0.00766
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
7.2
Dann
Benign
0.58

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs55709737; hg19: chr3-53217551; COSMIC: COSV57848982; COSMIC: COSV57848982; API