chr19-53881850-T-C

Position:

• chr19-53881850-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000474397.5(PRKCG):​c.-323+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 155,696 control chromosomes in the GnomAD database, including 61,248 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.88 (59691 hom., cov: 30)
  • Exomes 𝑓: 0.93 (1557 hom.)
• Consequence: PRKCG ENST00000474397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCG	XM_047439092.1	c.-323+10T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCG	ENST00000474397.5	c.-323+10T>C		intron_variant		5
PRKCG	ENST00000479081.5	c.-322-707T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134142 AN: 151990 Hom.: 59662 Cov.: 30

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.882

GnomAD4 exome AF: 0.931 AC: 3339 AN: 3588 Hom.: 1557 Cov.: 0 AF XY: 0.939 AC XY: 2031 AN XY: 2164

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.909

Gnomad4 ASJ exome AF: 0.972

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.956

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.922

Gnomad4 OTH exome AF: 0.905

GnomAD4 genome AF: 0.882 AC: 134228 AN: 152108 Hom.: 59691 Cov.: 30 AF XY: 0.885 AC XY: 65824 AN XY: 74358

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.962

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.926

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.883

Alfa AF: 0.913 Hom.: 36934

Bravo AF: 0.878

Asia WGS AF: 0.943 AC: 3280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs307941; hg19: chr19-54385104;