chr10-50991310-AGCCGCCGCC-A

Position:

• chr10-50991310-AGCCGCCGCC-A

Variant summary

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

The NM_001098512.3(PRKG1):​c.-44_-36del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,395,442 control chromosomes in the GnomAD database, including 41,943 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3021 hom., cov: 0)
  • Exomes 𝑓: 0.25 (38922 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.62

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 10-50991310-AGCCGCCGCC-A is Benign according to our data. Variant chr10-50991310-AGCCGCCGCC-A is described in ClinVar as [Benign]. Clinvar id is 1221009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3	c.-44_-36del		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8	c.-44_-36del		5_prime_UTR_variant	1/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 27206 AN: 143720 Hom.: 3019 Cov.: 0

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.252 AC: 315664 AN: 1251624 Hom.: 38922 AF XY: 0.253 AC XY: 156220 AN XY: 616680

Gnomad4 AFR exome AF: 0.0514

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.189 AC: 27213 AN: 143818 Hom.: 3021 Cov.: 0 AF XY: 0.195 AC XY: 13631 AN XY: 69830

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.213

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 18, 2019

- -

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: rs79957958; hg19: chr10-52751070;