rs55683301

Variant names:

• chr3-170281882-A-G
• rs55683301
• NM_002740.6:c.981A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002740.6(PRKCI):​c.981A>G​(p.Arg327Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,587,912 control chromosomes in the GnomAD database, including 430 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (41 hom., cov: 32)
  • Exomes 𝑓: 0.020 (389 hom.)
• Consequence: PRKCI NM_002740.6 splice_region, synonymous
• Scores: Splicing: ADA: 0.000002493
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 8 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.071 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCI	NM_002740.6	c.981A>G	p.Arg327Arg	splice_region_variant, synonymous_variant	Exon 11 of 18	ENST00000295797.5	NP_002731.4
PRKCI	XM_047448575.1	c.639A>G	p.Arg213Arg	splice_region_variant, synonymous_variant	Exon 10 of 17		XP_047304531.1
PRKCI	XM_047448574.1	c.981A>G	p.Arg327Arg	splice_region_variant, synonymous_variant	Exon 11 of 13		XP_047304530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCI	ENST00000295797.5	c.981A>G	p.Arg327Arg	splice_region_variant, synonymous_variant	Exon 11 of 18	1	NM_002740.6	ENSP00000295797.4
PRKCI	ENST00000482353.2	n.273A>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2359 AN: 152046 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0187 AC: 4332 AN: 231652 AF XY: 0.0182

Gnomad AFR exome AF: 0.00449

Gnomad AMR exome AF: 0.00507

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.0898

Gnomad FIN exome AF: 0.00836

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0154

GnomAD4 exome AF: 0.0199 AC: 28572 AN: 1435748 Hom.: 389 Cov.: 30 AF XY: 0.0193 AC XY: 13796 AN XY: 713520

African (AFR) AF: 0.00317 AC: 102 AN: 32196

American (AMR) AF: 0.00535 AC: 213 AN: 39804

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 421 AN: 25356

East Asian (EAS) AF: 0.0768 AC: 2971 AN: 38672

South Asian (SAS) AF: 0.00489 AC: 394 AN: 80530

European-Finnish (FIN) AF: 0.00880 AC: 463 AN: 52638

Middle Eastern (MID) AF: 0.00370 AC: 21 AN: 5674

European-Non Finnish (NFE) AF: 0.0207 AC: 22824 AN: 1101556

Other (OTH) AF: 0.0196 AC: 1163 AN: 59322

GnomAD4 genome AF: 0.0155 AC: 2358 AN: 152164 Hom.: 41 Cov.: 32 AF XY: 0.0149 AC XY: 1110 AN XY: 74380

African (AFR) AF: 0.00412 AC: 171 AN: 41530

American (AMR) AF: 0.00668 AC: 102 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3464

East Asian (EAS) AF: 0.0853 AC: 442 AN: 5182

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4822

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0190 AC: 1294 AN: 67978

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.0199 Hom.: 147

Bravo AF: 0.0154

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		0.071
Mutation Taster		=75/25	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000025
dbscSNV1_RF	Benign	0.014
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: rs55683301; hg19: chr3-169999670; COSMIC: COSV55522040; COSMIC: COSV55522040;