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GeneBe

3-170284492-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002740.6(PRKCI):c.1099A>G(p.Asn367Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRKCI
NM_002740.6 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.88
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCINM_002740.6 linkuse as main transcriptc.1099A>G p.Asn367Asp missense_variant 12/18 ENST00000295797.5
PRKCIXM_047448575.1 linkuse as main transcriptc.757A>G p.Asn253Asp missense_variant 11/17
PRKCIXM_047448574.1 linkuse as main transcriptc.1099A>G p.Asn367Asp missense_variant 12/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCIENST00000295797.5 linkuse as main transcriptc.1099A>G p.Asn367Asp missense_variant 12/181 NM_002740.6 P1
PRKCIENST00000482353.2 linkuse as main transcriptn.391A>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 14, 2023The c.1099A>G (p.N367D) alteration is located in exon 12 (coding exon 12) of the PRKCI gene. This alteration results from a A to G substitution at nucleotide position 1099, causing the asparagine (N) at amino acid position 367 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Benign
0.0036
T
BayesDel_noAF
Benign
-0.23
Cadd
Pathogenic
27
Dann
Uncertain
1.0
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.043
D
MetaRNN
Pathogenic
0.84
D
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
-0.20
N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-4.1
D
REVEL
Uncertain
0.42
Sift
Uncertain
0.028
D
Sift4G
Benign
0.21
T
Polyphen
1.0
D
Vest4
0.88
MutPred
0.34
Gain of relative solvent accessibility (P = 0.09);
MVP
0.83
MPC
0.90
ClinPred
0.99
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
gMVP
0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-170002280; API