Variant 19-53882302-TGGCGGAGCCGGCGCG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002739.5(PRKCG):c.-192_-178del 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. 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PRKCG	NM_002739.5 linkuse as main transcript	c.-192_-178del	5_prime_UTR_variant	1/18	ENST00000263431.4
PRKCG	NM_001316329.2 linkuse as main transcript	c.-192_-178del	5_prime_UTR_variant	1/19
PRKCG	XM_047439092.1 linkuse as main transcript	c.-322-254_-322-240del	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000263431.4 linkuse as main transcript	c.-192_-178del		5_prime_UTR_variant	1/18	1	NM_002739.5	P1	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

GnomAD3 exomes

AF:

0.00373

AC:

446

AN:

119658

Hom.:

AF XY:

0.00390

AC XY:

268

AN XY:

68748

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 SAS exome

AF:

0.0114

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

Gnomad4 AFR exome

AF:

0.000549

Gnomad4 AMR exome

AF:

0.00191

Gnomad4 ASJ exome

AF:

0.00242

Gnomad4 EAS exome

AF:

0.0000352

Gnomad4 SAS exome

AF:

0.00897

Gnomad4 FIN exome

AF:

0.000716

Gnomad4 NFE exome

AF:

0.00529

Gnomad4 OTH exome

AF:

0.00406

GnomAD4 genome

AF:

0.00231

AC:

351

AN:

152152

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00995

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00338

Gnomad4 OTH

AF:

0.00427

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 09, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over