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17-66688960-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_002737.3(PRKCA):c.831G>A(p.Leu277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,590,964 control chromosomes in the GnomAD database, including 95,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6907 hom., cov: 32)
Exomes 𝑓: 0.35 ( 89069 hom. )

Consequence

PRKCA
NM_002737.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.69
Variant links:
Genes affected
PRKCA (HGNC:9393): (protein kinase C alpha) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-66688960-G-A is Benign according to our data. Variant chr17-66688960-G-A is described in ClinVar as [Benign]. Clinvar id is 1295165.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=2.69 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCANM_002737.3 linkuse as main transcriptc.831G>A p.Leu277= synonymous_variant 8/17 ENST00000413366.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCAENST00000413366.8 linkuse as main transcriptc.831G>A p.Leu277= synonymous_variant 8/171 NM_002737.3 P1
PRKCAENST00000578063.5 linkuse as main transcriptc.831G>A p.Leu277= synonymous_variant, NMD_transcript_variant 8/101
PRKCAENST00000284384.6 linkuse as main transcriptc.*433G>A 3_prime_UTR_variant, NMD_transcript_variant 9/155

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.281
AC:
42653
AN:
151822
Hom.:
6904
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.120
Gnomad AMI
AF:
0.417
Gnomad AMR
AF:
0.299
Gnomad ASJ
AF:
0.416
Gnomad EAS
AF:
0.111
Gnomad SAS
AF:
0.339
Gnomad FIN
AF:
0.382
Gnomad MID
AF:
0.421
Gnomad NFE
AF:
0.358
Gnomad OTH
AF:
0.293
GnomAD3 exomes
AF:
0.316
AC:
77590
AN:
245280
Hom.:
13382
AF XY:
0.325
AC XY:
43058
AN XY:
132494
show subpopulations
Gnomad AFR exome
AF:
0.114
Gnomad AMR exome
AF:
0.298
Gnomad ASJ exome
AF:
0.420
Gnomad EAS exome
AF:
0.108
Gnomad SAS exome
AF:
0.352
Gnomad FIN exome
AF:
0.366
Gnomad NFE exome
AF:
0.355
Gnomad OTH exome
AF:
0.335
GnomAD4 exome
AF:
0.345
AC:
497127
AN:
1439026
Hom.:
89069
Cov.:
29
AF XY:
0.346
AC XY:
248210
AN XY:
716542
show subpopulations
Gnomad4 AFR exome
AF:
0.107
Gnomad4 AMR exome
AF:
0.300
Gnomad4 ASJ exome
AF:
0.420
Gnomad4 EAS exome
AF:
0.131
Gnomad4 SAS exome
AF:
0.354
Gnomad4 FIN exome
AF:
0.367
Gnomad4 NFE exome
AF:
0.359
Gnomad4 OTH exome
AF:
0.335
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.281
AC:
42661
AN:
151938
Hom.:
6907
Cov.:
32
AF XY:
0.283
AC XY:
21003
AN XY:
74230
show subpopulations
Gnomad4 AFR
AF:
0.119
Gnomad4 AMR
AF:
0.299
Gnomad4 ASJ
AF:
0.416
Gnomad4 EAS
AF:
0.111
Gnomad4 SAS
AF:
0.340
Gnomad4 FIN
AF:
0.382
Gnomad4 NFE
AF:
0.358
Gnomad4 OTH
AF:
0.296
Alfa
AF:
0.330
Hom.:
4912
Bravo
AF:
0.266
Asia WGS
AF:
0.240
AC:
836
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 17, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
10
Dann
Benign
0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs2227857; hg19: chr17-64685078; COSMIC: COSV52591389; API