chr17-66302841-T-TG

Variant names:

• chr17-66302841-T-TG
• rs759335653
• ENST00000578063.5:n.-4dupG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_002737.3(PRKCA):​c.-4dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,575,856 control chromosomes in the GnomAD database, including 11,361 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1248 hom., cov: 30)
  • Exomes 𝑓: 0.11 (10113 hom.)
• Consequence: PRKCA NM_002737.3 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0800
• Publications: 2 publications found

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]

ENSG00000307784 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 17-66302841-T-TG is Benign according to our data. Variant chr17-66302841-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 3056232.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.-4dupG		5_prime_UTR_variant	Exon 1 of 17	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.-4dupG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002737.3	ENSP00000408695.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18675 AN: 151002 Hom.: 1238 Cov.: 30

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.131 AC: 27312 AN: 208084 AF XY: 0.136

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.113 AC: 161323 AN: 1424742 Hom.: 10113 Cov.: 34 AF XY: 0.117 AC XY: 82557 AN XY: 707742

African (AFR) AF: 0.129 AC: 4011 AN: 30976

American (AMR) AF: 0.117 AC: 4785 AN: 40732

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2747 AN: 24948

East Asian (EAS) AF: 0.188 AC: 6846 AN: 36346

South Asian (SAS) AF: 0.220 AC: 18211 AN: 82936

European-Finnish (FIN) AF: 0.169 AC: 8643 AN: 51200

Middle Eastern (MID) AF: 0.122 AC: 687 AN: 5646

European-Non Finnish (NFE) AF: 0.0992 AC: 108413 AN: 1093244

Other (OTH) AF: 0.119 AC: 6980 AN: 58714

GnomAD4 genome AF: 0.124 AC: 18707 AN: 151114 Hom.: 1248 Cov.: 30 AF XY: 0.130 AC XY: 9581 AN XY: 73842

African (AFR) AF: 0.130 AC: 5386 AN: 41348

American (AMR) AF: 0.116 AC: 1767 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 393 AN: 3460

East Asian (EAS) AF: 0.162 AC: 820 AN: 5072

South Asian (SAS) AF: 0.225 AC: 1081 AN: 4802

European-Finnish (FIN) AF: 0.169 AC: 1730 AN: 10240

Middle Eastern (MID) AF: 0.114 AC: 33 AN: 290

European-Non Finnish (NFE) AF: 0.105 AC: 7104 AN: 67684

Other (OTH) AF: 0.131 AC: 275 AN: 2096

Alfa AF: 0.0720 Hom.: 112

Bravo AF: 0.116

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PRKCA-related disorder Benign:1

Jan 22, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.080
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs759335653; hg19: chr17-64298959;