rs9910577

Variant names:

• chr17-66318430-T-C
• rs9910577
• NM_002737.3:c.205+12303T>C

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+12303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,800 control chromosomes in the GnomAD database, including 26,403 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 0.59 (26403 hom., cov: 30)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.205+12303T>C		intron_variant	Intron 2 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.205+12303T>C		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.205+12303T>C		intron_variant	Intron 2 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.196+12303T>C		intron_variant	Intron 2 of 14	5		ENSP00000284384.6
PRKCA	ENST00000583361.1	n.249+12303T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89266 AN: 151682 Hom.: 26360 Cov.: 30

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.589 AC: 89369 AN: 151800 Hom.: 26403 Cov.: 30 AF XY: 0.589 AC XY: 43679 AN XY: 74158

African (AFR) AF: 0.624 AC: 25801 AN: 41376

American (AMR) AF: 0.585 AC: 8927 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3466

East Asian (EAS) AF: 0.569 AC: 2931 AN: 5148

South Asian (SAS) AF: 0.638 AC: 3064 AN: 4804

European-Finnish (FIN) AF: 0.572 AC: 6013 AN: 10514

Middle Eastern (MID) AF: 0.414 AC: 120 AN: 290

European-Non Finnish (NFE) AF: 0.578 AC: 39234 AN: 67932

Other (OTH) AF: 0.530 AC: 1115 AN: 2102

Alfa AF: 0.597 Hom.: 3509

Bravo AF: 0.588

Asia WGS AF: 0.616 AC: 2141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.40
DANN	Benign	0.52
PhyloP100		-1.8
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: rs9910577; hg19: chr17-64314548;