NM_002740.6:c.101+3542C>T

Variant names:

• chr3-170226312-C-T
• rs546950
• NM_002740.6:c.101+3542C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002740.6(PRKCI):​c.101+3542C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,074 control chromosomes in the GnomAD database, including 11,765 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 0.37 (11765 hom., cov: 33)
• Consequence: PRKCI NM_002740.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCI	NM_002740.6	c.101+3542C>T		intron_variant	Intron 1 of 17	ENST00000295797.5	NP_002731.4
PRKCI	XM_047448574.1	c.101+3542C>T		intron_variant	Intron 1 of 12		XP_047304530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCI	ENST00000295797.5	c.101+3542C>T		intron_variant	Intron 1 of 17	1	NM_002740.6	ENSP00000295797.4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56516 AN: 151956 Hom.: 11754 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.372 AC: 56558 AN: 152074 Hom.: 11765 Cov.: 33 AF XY: 0.379 AC XY: 28158 AN XY: 74302

African (AFR) AF: 0.167 AC: 6930 AN: 41504

American (AMR) AF: 0.451 AC: 6882 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1484 AN: 3472

East Asian (EAS) AF: 0.557 AC: 2877 AN: 5166

South Asian (SAS) AF: 0.435 AC: 2101 AN: 4826

European-Finnish (FIN) AF: 0.491 AC: 5171 AN: 10530

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29801 AN: 67992

Other (OTH) AF: 0.388 AC: 819 AN: 2110

Alfa AF: 0.427 Hom.: 27688

Bravo AF: 0.360

Asia WGS AF: 0.492 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.38
PhyloP100		-0.39
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: rs546950; hg19: chr3-169944100;