3-170240764-A-G

Variant names:

• chr3-170240764-A-G
• rs1684885
• NM_002740.6:c.223+5413A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002740.6. 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
	PRKCI	NM_002740.6	MANE Select	c.223+5413A>G		intron	N/A	NP_002731.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCI	ENST00000295797.5	TSL:1 MANE Select	c.223+5413A>G		intron	N/A	ENSP00000295797.4
	PRKCI	ENST00000904925.1		c.223+5413A>G		intron	N/A	ENSP00000574984.1
	PRKCI	ENST00000919187.1		c.223+5413A>G		intron	N/A	ENSP00000589246.1

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

African (AFR) AF: 0.829 AC: 34378 AN: 41494

American (AMR) AF: 0.819 AC: 12518 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2701 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4581 AN: 5186

South Asian (SAS) AF: 0.884 AC: 4267 AN: 4828

European-Finnish (FIN) AF: 0.865 AC: 9154 AN: 10588

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55058 AN: 67978

Other (OTH) AF: 0.776 AC: 1638 AN: 2110

Alfa AF: 0.811 Hom.: 100394

Bravo AF: 0.818

Asia WGS AF: 0.868 AC: 3017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.68
PhyloP100		-1.0
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: rs1684885; hg19: chr3-169958552;