rs10512510

Variant names:

• chr17-66371929-A-T
• rs10512510
• NM_002737.3:c.205+65802A>T

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+65802A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,250 control chromosomes in the GnomAD database, including 745 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 0.092 (745 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.205+65802A>T		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+65802A>T		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.205+65802A>T		intron_variant	Intron 2 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.196+65802A>T		intron_variant	Intron 2 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14053 AN: 152132 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0846

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

GnomAD4 genome AF: 0.0924 AC: 14071 AN: 152250 Hom.: 745 Cov.: 32 AF XY: 0.0899 AC XY: 6696 AN XY: 74452

African (AFR) AF: 0.134 AC: 5562 AN: 41544

American (AMR) AF: 0.0788 AC: 1206 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3468

East Asian (EAS) AF: 0.120 AC: 620 AN: 5184

South Asian (SAS) AF: 0.0924 AC: 445 AN: 4818

European-Finnish (FIN) AF: 0.0588 AC: 624 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5066 AN: 68014

Other (OTH) AF: 0.0875 AC: 185 AN: 2114

Alfa AF: 0.0843 Hom.: 80

Bravo AF: 0.0988

Asia WGS AF: 0.131 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.84
PhyloP100		-0.47
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: rs10512510; hg19: chr17-64368047;