rs307942

Variant names:

• chr19-53882183-A-C
• rs307942
• ENST00000474397.5:c.-323+343A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-53882183-A-C
• chr19-53882183-A-G
• chr19-53882183-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000479081.5(PRKCG):​c.-322-374A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 384,370 control chromosomes in the GnomAD database, including 181,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (72269 hom., cov: 31)
  • Exomes 𝑓: 0.97 (109323 hom.)
• Consequence: PRKCG ENST00000479081.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105
• Publications: 9 publications found

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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 19-53882183-A-C is Benign according to our data. Variant chr19-53882183-A-C is described in ClinVar as Benign. ClinVar VariationId is 1260463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479081.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	NM_002739.5	MANE Select	c.-312A>C		upstream_gene	N/A	NP_002730.1	P05129-1
	PRKCG	NM_001316329.2		c.-312A>C		upstream_gene	N/A	NP_001303258.1	A0A804HIU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCG	ENST00000474397.5	TSL:5	c.-323+343A>C		intron	N/A	ENSP00000471271.1	M0R0I9
	PRKCG	ENST00000479081.5	TSL:4	c.-322-374A>C		intron	N/A	ENSP00000471544.1	M0R0Z4
	PRKCG	ENST00000263431.4	TSL:1 MANE Select	c.-312A>C		upstream_gene	N/A	ENSP00000263431.3	P05129-1

Frequencies

GnomAD3 genomes AF: 0.974 AC: 148173 AN: 152084 Hom.: 72211 Cov.: 31

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.970

GnomAD2 exomes AF: 0.967 AC: 12212 AN: 12626 AF XY: 0.968

Gnomad AFR exome AF: 0.985

Gnomad AMR exome AF: 0.976

Gnomad ASJ exome AF: 0.972

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.962

Gnomad NFE exome AF: 0.951

Gnomad OTH exome AF: 0.977

GnomAD4 exome AF: 0.970 AC: 225275 AN: 232170 Hom.: 109323 Cov.: 2 AF XY: 0.973 AC XY: 123965 AN XY: 127414

African (AFR) AF: 0.993 AC: 3741 AN: 3766

American (AMR) AF: 0.978 AC: 5377 AN: 5498

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 6449 AN: 6538

East Asian (EAS) AF: 1.00 AC: 7629 AN: 7632

South Asian (SAS) AF: 0.993 AC: 38162 AN: 38420

European-Finnish (FIN) AF: 0.962 AC: 14201 AN: 14766

Middle Eastern (MID) AF: 0.977 AC: 1754 AN: 1796

European-Non Finnish (NFE) AF: 0.961 AC: 135531 AN: 140964

Other (OTH) AF: 0.972 AC: 12431 AN: 12790

GnomAD4 genome AF: 0.974 AC: 148289 AN: 152200 Hom.: 72269 Cov.: 31 AF XY: 0.974 AC XY: 72501 AN XY: 74404

African (AFR) AF: 0.993 AC: 41261 AN: 41550

American (AMR) AF: 0.976 AC: 14928 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3437 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5141 AN: 5142

South Asian (SAS) AF: 0.995 AC: 4806 AN: 4828

European-Finnish (FIN) AF: 0.964 AC: 10230 AN: 10614

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.961 AC: 65332 AN: 67976

Other (OTH) AF: 0.970 AC: 2051 AN: 2114

Alfa AF: 0.947 Hom.: 3166

Bravo AF: 0.976

Asia WGS AF: 0.996 AC: 3463 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.47
PhyloP100		0.10
PromoterAI		-0.0040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs307942; hg19: chr19-54385437;