3-170244472-T-C

Variant names:

• chr3-170244472-T-C
• rs1684881
• NM_002740.6:c.223+9121T>C

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+9121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,056 control chromosomes in the GnomAD database, including 51,660 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 (51660 hom., cov: 30)
• Consequence: PRKCI NM_002740.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCI	NM_002740.6	c.223+9121T>C		intron_variant	Intron 2 of 17	ENST00000295797.5	NP_002731.4
PRKCI	XM_047448574.1	c.223+9121T>C		intron_variant	Intron 2 of 12		XP_047304530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCI	ENST00000295797.5	c.223+9121T>C		intron_variant	Intron 2 of 17	1	NM_002740.6	ENSP00000295797.4

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125120 AN: 151938 Hom.: 51619 Cov.: 30

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.823 AC: 125214 AN: 152056 Hom.: 51660 Cov.: 30 AF XY: 0.826 AC XY: 61428 AN XY: 74330

African (AFR) AF: 0.823 AC: 34111 AN: 41466

American (AMR) AF: 0.823 AC: 12561 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2706 AN: 3472

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

South Asian (SAS) AF: 0.886 AC: 4263 AN: 4814

European-Finnish (FIN) AF: 0.864 AC: 9130 AN: 10564

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55191 AN: 67984

Other (OTH) AF: 0.778 AC: 1641 AN: 2108

Alfa AF: 0.819 Hom.: 23593

Bravo AF: 0.818

Asia WGS AF: 0.870 AC: 3021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1684881; hg19: chr3-169962260;