19-53882673-A-T

Position:

• chr19-53882673-A-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_002739.5(PRKCG):​c.170+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKCG NM_002739.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.320

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-53882673-A-T is Benign according to our data. Variant chr19-53882673-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038206.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-53882673-A-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCG	NM_002739.5	c.170+9A>T		intron_variant		ENST00000263431.4
PRKCG	NM_001316329.2	c.170+9A>T		intron_variant
PRKCG	XM_047439092.1	c.-215+9A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000263431.4	c.170+9A>T		intron_variant		1	NM_002739.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15 AN: 143158 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000688

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000954

Gnomad SAS AF: 0.000254

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000769

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00198 AC: 1703 AN: 858914 Hom.: 0 Cov.: 39 AF XY: 0.00187 AC XY: 819 AN XY: 438054

Gnomad4 AFR exome AF: 0.00349

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00366

Gnomad4 EAS exome AF: 0.00381

Gnomad4 SAS exome AF: 0.000302

Gnomad4 FIN exome AF: 0.000665

Gnomad4 NFE exome AF: 0.00210

Gnomad4 OTH exome AF: 0.00343

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000105 AC: 15 AN: 143310 Hom.: 0 Cov.: 31 AF XY: 0.000129 AC XY: 9 AN XY: 69726

Gnomad4 AFR AF: 0.000100

Gnomad4 AMR AF: 0.0000686

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000954

Gnomad4 SAS AF: 0.000252

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000769

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PRKCG-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54385927;