rs557551763

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002739.5(PRKCG):c.-192_-178delGGCGGAGCCGGCGCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 776,034 control chromosomes in the GnomAD database, including 12 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 11 hom. )

Consequence

PRKCG
NM_002739.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.47

Publications

0 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 -10 ACMG points.

BP6

Variant 19-53882302-TGGCGGAGCCGGCGCG-T is Benign according to our data. Variant chr19-53882302-TGGCGGAGCCGGCGCG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2579987.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00231 (351/152152) while in subpopulation SAS AF = 0.00995 (48/4822). AF 95% confidence interval is 0.00771. There are 1 homozygotes in GnomAd4. There are 148 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRKCG	NM_002739.5 link	c.-192_-178delGGCGGAGCCGGCGCG	5_prime_UTR_variant	Exon 1 of 18	ENST00000263431.4	NP_002730.1	P05129-1
PRKCG	NM_001316329.2 link	c.-192_-178delGGCGGAGCCGGCGCG	5_prime_UTR_variant	Exon 1 of 19		NP_001303258.1	P05129B7Z3W6B2R5T1A0A804HIU5
PRKCG	XM_047439092.1 link	c.-322-254_-322-240delGGCGGAGCCGGCGCG	intron_variant	Intron 1 of 19		XP_047295048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4 link	c.-192_-178delGGCGGAGCCGGCGCG		5_prime_UTR_variant	Exon 1 of 18	1	NM_002739.5	ENSP00000263431.3		P05129-1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

351

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00995

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00338

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00373

AC:

446

AN:

119658

AF XY:

0.00390

show subpopulations

Gnomad AFR exome

AF:

0.000269

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.000125

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00370

Gnomad OTH exome

AF:

0.00383

GnomAD4 exome

AF:

0.00476

AC:

2968

AN:

623882

Hom.:

AF XY:

0.00478

AC XY:

1579

AN XY:

330130

show subpopulations

African (AFR)

AF:

0.000549

AC:

AN:

12746

American (AMR)

AF:

0.00191

AC:

AN:

21976

Ashkenazi Jewish (ASJ)

AF:

0.00242

AC:

AN:

15308

East Asian (EAS)

AF:

0.0000352

AC:

AN:

28404

South Asian (SAS)

AF:

0.00897

AC:

501

AN:

55832

European-Finnish (FIN)

AF:

0.000716

AC:

AN:

36296

Middle Eastern (MID)

AF:

0.00390

AC:

AN:

3844

European-Non Finnish (NFE)

AF:

0.00529

AC:

2213

AN:

418452

Other (OTH)

AF:

0.00406

AC:

126

AN:

31024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

138

275

413

550

688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.00231

AC:

351

AN:

152152

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41550

American (AMR)

AF:

0.00183

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00995

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00338

AC:

230

AN:

67970

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00230

Hom.:

Bravo

AF:

0.00246

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 09, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Mutation Taster

=297/3

polymorphism

(source)

Splicing

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