3-170240764-A-G

Position:

• chr3-170240764-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002740.6(PRKCI):​c.223+5413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,140 control chromosomes in the GnomAD database, including 51,698 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 0.82 (51698 hom., cov: 32)
• Consequence: PRKCI NM_002740.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

PRKCI (HGNC:9404): (protein kinase C iota) This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCI	NM_002740.6	c.223+5413A>G		intron_variant		ENST00000295797.5
PRKCI	XM_047448574.1	c.223+5413A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCI	ENST00000295797.5	c.223+5413A>G		intron_variant		1	NM_002740.6	P1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125227 AN: 152022 Hom.: 51657 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.824 AC: 125321 AN: 152140 Hom.: 51698 Cov.: 32 AF XY: 0.826 AC XY: 61467 AN XY: 74386

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.776

Alfa AF: 0.810 Hom.: 72689

Bravo AF: 0.818

Asia WGS AF: 0.868 AC: 3017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1684885; hg19: chr3-169958552;