dbSNP rs3795277: PRKCZ-DT:n.498T>G (chr1-2049679-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000445600.2(PRKCZ-DT):n.498T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,458 control chromosomes in the GnomAD database, including 699 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.083 ( 697 hom., cov: 33)

Exomes 𝑓: 0.084 ( 2 hom. )

Consequence

PRKCZ-DT
ENST00000445600.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.350

Publications

4 publications found

Variant links:

Genes affected

PRKCZ-DT (HGNC:55824): (PRKCZ divergent transcript)

PRKCZ-DT links:

PRKCZ (HGNC:9412): (protein kinase C zeta) Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

PRKCZ links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCZ-DT	NR_135509.1 link	n.204-13T>G		intron_variant	Intron 1 of 2
PRKCZ	XM_047425255.1 link	c.56+1004A>C		intron_variant	Intron 1 of 17		XP_047281211.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PRKCZ-DT	ENST00000445600.2 link	n.498T>G	non_coding_transcript_exon_variant	Exon 1 of 2	3
PRKCZ-DT	ENST00000449154.1 link	n.204-13T>G	intron_variant	Intron 1 of 2	3
PRKCZ-DT	ENST00000776845.1 link	n.309+189T>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0829

AC:

12596

AN:

152018

Hom.:

694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0871

Gnomad OTH

AF:

0.0825

GnomAD4 exome

AF:

0.0839

AC:

AN:

322

Hom.:

Cov.:

AF XY:

0.0796

AC XY:

AN XY:

226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.115

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0909

AC:

AN:

242

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0829

AC:

12608

AN:

152136

Hom.:

697

Cov.:

AF XY:

0.0868

AC XY:

6457

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0403

AC:

1675

AN:

41530

American (AMR)

AF:

0.0885

AC:

1354

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0536

AC:

186

AN:

3468

East Asian (EAS)

AF:

0.261

AC:

1343

AN:

5136

South Asian (SAS)

AF:

0.149

AC:

716

AN:

4818

European-Finnish (FIN)

AF:

0.109

AC:

1156

AN:

10606

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0871

AC:

5919

AN:

67972

Other (OTH)

AF:

0.0854

AC:

180

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

617

1234

1851

2468

3085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.0822

Hom.:

618

Bravo

AF:

0.0803

Asia WGS

AF:

0.239

AC:

830

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.1

(source)

DANN

Benign

0.61

PhyloP100

0.35

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over