chr10-50991328-C-CGCT

Position:

• chr10-50991328-C-CGCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001098512.3(PRKG1):​c.-49_-48insTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,476,694 control chromosomes in the GnomAD database, including 38,643 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4524 hom., cov: 23)
  • Exomes 𝑓: 0.24 (34119 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.205

Genes affected

PRKG1 (HGNC:9414): (protein kinase cGMP-dependent 1) Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-50991328-C-CGCT is Benign according to our data. Variant chr10-50991328-C-CGCT is described in ClinVar as [Benign]. Clinvar id is 1266074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3	c.-49_-48insTGC		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8	c.-49_-48insTGC		5_prime_UTR_variant	1/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35897 AN: 151432 Hom.: 4527 Cov.: 23

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.237 AC: 314042 AN: 1325150 Hom.: 34119 Cov.: 35 AF XY: 0.234 AC XY: 152830 AN XY: 652590

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.237 AC: 35896 AN: 151544 Hom.: 4524 Cov.: 23 AF XY: 0.236 AC XY: 17474 AN XY: 74006

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.243

Alfa AF: 0.0853 Hom.: 127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

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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: rs35361017; hg19: chr10-52751088;