19-53900547-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002739.5(PRKCG):c.1437-64T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,614,186 control chromosomes in the GnomAD database, including 997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 193 hom., cov: 32)

Exomes 𝑓: 0.015 ( 804 hom. )

Consequence

PRKCG
NM_002739.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.34

Publications

11 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

PRKCG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 19-53900547-T-C is Benign according to our data. Variant chr19-53900547-T-C is described in CliVar as Benign. Clinvar id is 1270032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53900547-T-C is described in CliVar as Benign. Clinvar id is 1270032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53900547-T-C is described in CliVar as Benign. Clinvar id is 1270032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53900547-T-C is described in CliVar as Benign. Clinvar id is 1270032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53900547-T-C is described in CliVar as Benign. Clinvar id is 1270032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRKCG	NM_002739.5 link	c.1437-64T>C	intron_variant	Intron 13 of 17	ENST00000263431.4	NP_002730.1	P05129-1
PRKCG	NM_001316329.2 link	c.1437-64T>C	intron_variant	Intron 13 of 18		NP_001303258.1	P05129B7Z3W6B2R5T1A0A804HIU5
PRKCG	XM_047439092.1 link	c.1053-64T>C	intron_variant	Intron 14 of 19		XP_047295048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4 link	c.1437-64T>C		intron_variant	Intron 13 of 17	1	NM_002739.5	ENSP00000263431.3		P05129-1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5041

AN:

152204

Hom.:

193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0786

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00550

Gnomad OTH

AF:

0.0330

GnomAD4 exome

AF:

0.0151

AC:

22077

AN:

1461864

Hom.:

804

Cov.:

AF XY:

0.0153

AC XY:

11126

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0786

AC:

2630

AN:

33480

American (AMR)

AF:

0.0465

AC:

2079

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00631

AC:

165

AN:

26136

East Asian (EAS)

AF:

0.151

AC:

5983

AN:

39700

South Asian (SAS)

AF:

0.0419

AC:

3618

AN:

86258

European-Finnish (FIN)

AF:

0.00382

AC:

204

AN:

53406

Middle Eastern (MID)

AF:

0.0264

AC:

152

AN:

5768

European-Non Finnish (NFE)

AF:

0.00533

AC:

5929

AN:

1111996

Other (OTH)

AF:

0.0218

AC:

1317

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1513

3025

4538

6050

7563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.0332

AC:

5051

AN:

152322

Hom.:

193

Cov.:

AF XY:

0.0338

AC XY:

2521

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0787

AC:

3273

AN:

41566

American (AMR)

AF:

0.0264

AC:

404

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.121

AC:

627

AN:

5178

South Asian (SAS)

AF:

0.0503

AC:

243

AN:

4830

European-Finnish (FIN)

AF:

0.00282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00550

AC:

374

AN:

68034

Other (OTH)

AF:

0.0326

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

239

479

718

958

1197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0213

Hom.:

136

Bravo

AF:

0.0375

Asia WGS

AF:

0.104

AC:

360

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 21, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.0050

(source)

DANN

Benign

0.29

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over