Menu
GeneBe

3-170281180-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002740.6(PRKCI):c.897A>C(p.Val299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 0 hom. )

Consequence

PRKCI
NM_002740.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-170281180-A-C is Benign according to our data. Variant chr3-170281180-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3033589.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.2 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 190 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCINM_002740.6 linkuse as main transcriptc.897A>C p.Val299= synonymous_variant 10/18 ENST00000295797.5
PRKCIXM_047448575.1 linkuse as main transcriptc.555A>C p.Val185= synonymous_variant 9/17
PRKCIXM_047448574.1 linkuse as main transcriptc.897A>C p.Val299= synonymous_variant 10/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCIENST00000295797.5 linkuse as main transcriptc.897A>C p.Val299= synonymous_variant 10/181 NM_002740.6 P1
PRKCIENST00000488541.1 linkuse as main transcriptn.274A>C non_coding_transcript_exon_variant 2/22
PRKCIENST00000493761.1 linkuse as main transcriptn.179A>C non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00125
AC:
190
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00254
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00200
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00119
AC:
299
AN:
251362
Hom.:
0
AF XY:
0.00126
AC XY:
171
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00282
Gnomad NFE exome
AF:
0.00194
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.00172
AC:
2519
AN:
1460794
Hom.:
0
Cov.:
30
AF XY:
0.00166
AC XY:
1208
AN XY:
726748
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00347
Gnomad4 NFE exome
AF:
0.00202
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00125
AC:
190
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.00111
AC XY:
83
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00254
Gnomad4 NFE
AF:
0.00200
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00156
Hom.:
0
Bravo
AF:
0.000918
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000927
EpiControl
AF:
0.00196

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PRKCI-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 10, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
0.37
Dann
Benign
0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138910174; hg19: chr3-169998968; API