19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T

Position:

• chr19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The ENST00000263431.4(PRKCG):​c.2091_*98del variant causes a stop lost, 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PRKCG ENST00000263431.4 stop_lost, 3_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 3.56

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in ENST00000263431.4 Downstream stopcodon found after 70 codons.
• PP5: Variant 19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T is Pathogenic according to our data. Variant chr19-53906891-TGTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 13252.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCG	NM_002739.5	c.2091_*98del		stop_lost, 3_prime_UTR_variant	18/18	ENST00000263431.4	NP_002730.1
PRKCG	NM_001316329.2	c.2090+1_2091-1del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001303258.1
PRKCG	XM_047439092.1	c.1706+1_1707-1del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_047295048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCG	ENST00000263431.4	c.2091_*98del		stop_lost, 3_prime_UTR_variant	18/18	1	NM_002739.5	ENSP00000263431	P1
PRKCG	ENST00000683513.1			coding_sequence_variant, 3_prime_UTR_variant	17/17			ENSP00000506809
PRKCG	ENST00000682028.1	c.2090+1_2091-1del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000507230
PRKCG	ENST00000682676.1	n.1492_1593del		non_coding_transcript_exon_variant	10/10

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Spinocerebellar ataxia type 14 Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 01, 2009	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555808841; hg19: chr19-54410145;