NM_002737.3:c.205+60955G>A

Variant names:

• chr17-66367082-G-A
• rs4411531
• NM_002737.3:c.205+60955G>A

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+60955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,178 control chromosomes in the GnomAD database, including 1,587 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 0.13 (1587 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.932
• Publications: 9 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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.205+60955G>A		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+60955G>A		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.205+60955G>A		intron_variant	Intron 2 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.196+60955G>A		intron_variant	Intron 2 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19969 AN: 152060 Hom.: 1584 Cov.: 32

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.131 AC: 19979 AN: 152178 Hom.: 1587 Cov.: 32 AF XY: 0.138 AC XY: 10287 AN XY: 74398

African (AFR) AF: 0.0654 AC: 2715 AN: 41528

American (AMR) AF: 0.218 AC: 3341 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1469 AN: 5162

South Asian (SAS) AF: 0.197 AC: 950 AN: 4814

European-Finnish (FIN) AF: 0.160 AC: 1698 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8672 AN: 68006

Other (OTH) AF: 0.155 AC: 328 AN: 2112

Alfa AF: 0.130 Hom.: 2248

Bravo AF: 0.131

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.3
DANN	Benign	0.59
PhyloP100		0.93
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: rs4411531; hg19: chr17-64363200;