14-61242375-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000555185.5(PRKCH):​c.-19+54707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,292 control chromosomes in the GnomAD database, including 67,312 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 0.94 ( 67312 hom., cov: 32)

Consequence

PRKCH
ENST00000555185.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.565
Variant links:
Genes affected
PRKCH (HGNC:9403): (protein kinase C eta) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the 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 family members 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 a distinct role in cells. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene. Mutations in this gene are associated with susceptibility to cerebral infarction. [provided by RefSeq, Sep 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKCHXM_024449661.2 linkc.-121+54707A>G intron_variant Intron 1 of 13 XP_024305429.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKCHENST00000555185.5 linkc.-19+54707A>G intron_variant Intron 1 of 3 3 ENSP00000451871.1 G3V4L3
PRKCHENST00000556778.5 linkc.-57+54707A>G intron_variant Intron 1 of 5 4 ENSP00000452055.1 G3V4X4
PRKCHENST00000557294.5 linkc.-109+54707A>G intron_variant Intron 1 of 1 4 ENSP00000452129.1 G3V520

Frequencies

GnomAD3 genomes
AF:
0.935
AC:
142349
AN:
152174
Hom.:
67266
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.781
Gnomad AMI
AF:
0.997
Gnomad AMR
AF:
0.975
Gnomad ASJ
AF:
0.995
Gnomad EAS
AF:
0.975
Gnomad SAS
AF:
0.992
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.972
Gnomad NFE
AF:
0.999
Gnomad OTH
AF:
0.947
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.935
AC:
142451
AN:
152292
Hom.:
67312
Cov.:
32
AF XY:
0.938
AC XY:
69858
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.781
Gnomad4 AMR
AF:
0.975
Gnomad4 ASJ
AF:
0.995
Gnomad4 EAS
AF:
0.975
Gnomad4 SAS
AF:
0.992
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
0.999
Gnomad4 OTH
AF:
0.947
Alfa
AF:
0.974
Hom.:
3478
Bravo
AF:
0.927
Asia WGS
AF:
0.968
AC:
3366
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.88
DANN
Benign
0.60

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.

Other links and lift over

dbSNP: rs1959660; hg19: chr14-61709093; API