rs1139537

Variant names:

• chr14-61549902-G-A
• rs1139537
• NM_006255.5:c.*71G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-61549902-G-A
• chr14-61549902-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006255.5(PRKCH):​c.*71G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PRKCH NM_006255.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 0 publications found

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]

ENSG00000258989 (HGNC:):

LINC01303 (HGNC:50470): (long intergenic non-protein coding RNA 1303)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCH	NM_006255.5	c.*71G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000332981.11	NP_006246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCH	ENST00000332981.11	c.*71G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_006255.5	ENSP00000329127.5
ENSG00000258989	ENST00000556347.1	c.417+2016G>A		intron_variant	Intron 3 of 3	4		ENSP00000452401.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367618 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 679544

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30536

American (AMR) AF: 0.00 AC: 0 AN: 36776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23226

East Asian (EAS) AF: 0.00 AC: 0 AN: 39074

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 77860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5412

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052106

Other (OTH) AF: 0.00 AC: 0 AN: 56886

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.34
PhyloP100		0.32

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

Other links and lift over

dbSNP: rs1139537; hg19: chr14-62016620;