NM_002737.3:c.205+81831A>G

Variant names:

• chr17-66387958-A-G
• rs17634425
• NM_002737.3:c.205+81831A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002737.3(PRKCA):​c.205+81831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,214 control chromosomes in the GnomAD database, including 755 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 0.093 (755 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002737.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	NM_002737.3	MANE Select	c.205+81831A>G		intron	N/A	NP_002728.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.205+81831A>G		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000578063.5	TSL:1	n.205+81831A>G		intron	N/A	ENSP00000462087.1
	PRKCA	ENST00000882063.1		c.205+81831A>G		intron	N/A	ENSP00000552122.1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14128 AN: 152096 Hom.: 751 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0866

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0929 AC: 14146 AN: 152214 Hom.: 755 Cov.: 33 AF XY: 0.0904 AC XY: 6728 AN XY: 74412

African (AFR) AF: 0.135 AC: 5588 AN: 41534

American (AMR) AF: 0.0787 AC: 1204 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3468

East Asian (EAS) AF: 0.119 AC: 615 AN: 5164

South Asian (SAS) AF: 0.0920 AC: 444 AN: 4826

European-Finnish (FIN) AF: 0.0589 AC: 625 AN: 10606

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5087 AN: 68008

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0810 Hom.: 939

Bravo AF: 0.0992

Asia WGS AF: 0.130 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.99
DANN	Benign	0.75
PhyloP100		-0.0090
Mutation Taster		=100/0	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: rs17634425; hg19: chr17-64384076;