chr17-66688966-C-T

Position:

• chr17-66688966-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.75

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 919 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.837C>T	p.Asn279Asn	synonymous_variant	8/17	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.837C>T	p.Asn279Asn	synonymous_variant	8/17	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.837C>T		non_coding_transcript_exon_variant	8/10	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.*439C>T		non_coding_transcript_exon_variant	9/15	5		ENSP00000284384.6
PRKCA	ENST00000284384.6	n.*439C>T		3_prime_UTR_variant	9/15	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.00602 AC: 915 AN: 151954 Hom.: 14 Cov.: 32

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

GnomAD3 exomes AF: 0.00230 AC: 568 AN: 246852 Hom.: 5 AF XY: 0.00190 AC XY: 253 AN XY: 133382

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 SAS exome AF: 0.000376

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.: 15 Cov.: 30 AF XY: 0.00106 AC XY: 769 AN XY: 722332

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.00258

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000424

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000464

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome AF: 0.00604 AC: 919 AN: 152072 Hom.: 14 Cov.: 32 AF XY: 0.00588 AC XY: 437 AN XY: 74340

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00393

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00380 Hom.: 3

Bravo AF: 0.00708

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00215

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs150522438; hg19: chr17-64685084;