dbSNP rs385039: PRKCZ:c.553-57A>G (chr1-2145970-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002744.6(PRKCZ):c.553-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,461,188 control chromosomes in the GnomAD database, including 55,510 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 0.24 ( 4876 hom., cov: 32)

Exomes 𝑓: 0.27 ( 50634 hom. )

Consequence

PRKCZ
NM_002744.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.51

Publications

17 publications found

Variant links:

Genes affected

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=-0.99).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCZ	NM_002744.6 link	c.553-57A>G		intron_variant	Intron 6 of 17	ENST00000378567.8	NP_002735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCZ	ENST00000378567.8 link	c.553-57A>G		intron_variant	Intron 6 of 17	1	NM_002744.6	ENSP00000367830.3

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35854

AN:

152070

Hom.:

4873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.237

GnomAD4 exome

AF:

0.274

AC:

358766

AN:

1309000

Hom.:

50634

AF XY:

0.275

AC XY:

181065

AN XY:

658572

show subpopulations

African (AFR)

AF:

0.0969

AC:

2908

AN:

30006

American (AMR)

AF:

0.386

AC:

16785

AN:

43440

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

7476

AN:

25064

East Asian (EAS)

AF:

0.184

AC:

7153

AN:

38918

South Asian (SAS)

AF:

0.290

AC:

24022

AN:

82780

European-Finnish (FIN)

AF:

0.305

AC:

16096

AN:

52764

Middle Eastern (MID)

AF:

0.220

AC:

1206

AN:

5484

European-Non Finnish (NFE)

AF:

0.276

AC:

269055

AN:

975316

Other (OTH)

AF:

0.255

AC:

14065

AN:

55228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

12589

25179

37768

50358

62947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8478

16956

25434

33912

42390

<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:

0.236

AC:

35878

AN:

152188

Hom.:

4876

Cov.:

AF XY:

0.240

AC XY:

17871

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0998

AC:

4147

AN:

41550

American (AMR)

AF:

0.332

AC:

5075

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1071

AN:

3470

East Asian (EAS)

AF:

0.195

AC:

1010

AN:

5176

South Asian (SAS)

AF:

0.288

AC:

1389

AN:

4818

European-Finnish (FIN)

AF:

0.311

AC:

3291

AN:

10578

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19093

AN:

67988

Other (OTH)

AF:

0.240

AC:

508

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1376

2753

4129

5506

6882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.265

Hom.:

7957

Bravo

AF:

0.231

Asia WGS

AF:

0.201

AC:

697

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.25

(source)

DANN

Benign

0.32

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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