chr17-66688966-C-T

Variant names:

Variant summary

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

The NM_002737.3(PRKCA):c.837C>T(p.Asn279Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,603,624 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

PRKCA
NM_002737.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.75

Publications

2 publications found

Variant links:

Genes affected

PRKCA (HGNC:9393): (protein kinase C alpha) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]

PRKCA links:

Genome browser will be placed here

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=-0.33).

BP6

Variant 17-66688966-C-T is Benign according to our data. Variant chr17-66688966-C-T is described in ClinVar as [Benign]. Clinvar id is 790185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.75 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00604 (919/152072) while in subpopulation AFR AF = 0.019 (787/41460). AF 95% confidence interval is 0.0179. There are 14 homozygotes in GnomAd4. There are 437 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 919 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3 link	c.837C>T	p.Asn279Asn	synonymous_variant	Exon 8 of 17	ENST00000413366.8	NP_002728.2	P17252L7RSM7Q7Z727

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRKCA	ENST00000413366.8 link	c.837C>T	p.Asn279Asn	synonymous_variant	Exon 8 of 17	1	NM_002737.3	ENSP00000408695.3	P17252
PRKCA	ENST00000578063.5 link	n.837C>T		non_coding_transcript_exon_variant	Exon 8 of 10	1		ENSP00000462087.1	J3KRN5
PRKCA	ENST00000284384.6 link	n.*439C>T		non_coding_transcript_exon_variant	Exon 9 of 15	5		ENSP00000284384.6	J3KN97
PRKCA	ENST00000284384.6 link	n.*439C>T		3_prime_UTR_variant	Exon 9 of 15	5		ENSP00000284384.6	J3KN97

Frequencies

GnomAD3 genomes

AF:

0.00602

AC:

915

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00862

GnomAD2 exomes

AF:

0.00230

AC:

568

AN:

246852

AF XY:

0.00190

show subpopulations

Gnomad AFR exome

AF:

0.0194

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.00260

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.00113

AC:

1636

AN:

1451552

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

769

AN XY:

722332

show subpopulations

African (AFR)

AF:

0.0198

AC:

658

AN:

33222

American (AMR)

AF:

0.00258

AC:

113

AN:

43830

Ashkenazi Jewish (ASJ)

AF:

0.00250

AC:

AN:

26020

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.000424

AC:

AN:

84872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000464

AC:

513

AN:

1104898

Other (OTH)

AF:

0.00293

AC:

176

AN:

60016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

140

211

281

351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00604

AC:

919

AN:

152072

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

437

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0190

AC:

787

AN:

41460

American (AMR)

AF:

0.00393

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

67996

Other (OTH)

AF:

0.00853

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00736

Hom.:

Bravo

AF:

0.00708

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00215

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

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chr17-66688966-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over