19-53884243-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002739.5(PRKCG):c.285C>T(p.Asp95Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,613,684 control chromosomes in the GnomAD database, including 467 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 230 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 237 hom. )

Consequence

PRKCG
NM_002739.5 splice_region, synonymous

Scores

Splicing: ADA: 0.004953

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.272

Publications

8 publications found

Variant links:

Genes affected

PRKCG (HGNC:9402): (protein kinase C gamma) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and 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 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 distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PRKCG Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 14
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

PRKCG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.085).

BP6

Variant 19-53884243-C-T is Benign according to our data. Variant chr19-53884243-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 330058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.272 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002739.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	NM_002739.5	MANE Select	c.285C>T	p.Asp95Asp	splice_region synonymous	Exon 3 of 18	NP_002730.1	P05129-1
	PRKCG	NM_001316329.2		c.285C>T	p.Asp95Asp	splice_region synonymous	Exon 3 of 19	NP_001303258.1	A0A804HIU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKCG	ENST00000263431.4	TSL:1 MANE Select	c.285C>T	p.Asp95Asp	splice_region synonymous	Exon 3 of 18	ENSP00000263431.3	P05129-1
PRKCG	ENST00000474397.5	TSL:5	c.-100C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 7	ENSP00000471271.1	M0R0I9
PRKCG	ENST00000419486.1	TSL:4	c.-100C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 6	ENSP00000387919.2	H7BZ60

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4737

AN:

152128

Hom.:

229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0998

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0115

AC:

2887

AN:

251378

AF XY:

0.00918

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00493

AC:

7208

AN:

1461438

Hom.:

237

Cov.:

AF XY:

0.00457

AC XY:

3323

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.106

AC:

3539

AN:

33468

American (AMR)

AF:

0.0144

AC:

642

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

305

AN:

26136

East Asian (EAS)

AF:

0.00564

AC:

224

AN:

39700

South Asian (SAS)

AF:

0.00175

AC:

151

AN:

86224

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.0225

AC:

123

AN:

5468

European-Non Finnish (NFE)

AF:

0.00136

AC:

1510

AN:

1111958

Other (OTH)

AF:

0.0118

AC:

711

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

410

820

1230

1640

2050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0312

AC:

4755

AN:

152246

Hom.:

230

Cov.:

AF XY:

0.0305

AC XY:

2267

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.100

AC:

4153

AN:

41538

American (AMR)

AF:

0.0167

AC:

255

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.0106

AC:

AN:

5174

South Asian (SAS)

AF:

0.00207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

68022

Other (OTH)

AF:

0.0341

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

218

436

653

871

1089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0130

Hom.:

162

Bravo

AF:

0.0358

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00338

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Spinocerebellar ataxia type 14 (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

0.27

Mutation Taster

=75/25

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0050

dbscSNV1_RF

Benign

0.14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over