10-50991310-AGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC

Variant names:

• chr10-50991310-A-AGCCGCCGCCGCCGCC
• rs79957958
• NM_001098512.3:c.-50_-36dupGCCGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001098512.3(PRKG1):​c.-50_-36dupGCCGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 460 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_001098512.3	c.-50_-36dupGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 18		NP_001091982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000401604	c.-50_-36dupGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000384200.4

Frequencies

GnomAD3 genomes AF: 0.00319 AC: 459 AN: 143814 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00254

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00114

Gnomad SAS AF: 0.000881

Gnomad FIN AF: 0.00298

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.00481

Gnomad OTH AF: 0.00357

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00190 AC: 2379 AN: 1251878 Hom.: 1 Cov.: 13 AF XY: 0.00187 AC XY: 1153 AN XY: 617018

Gnomad4 AFR exome AF: 0.000551

Gnomad4 AMR exome AF: 0.0000850

Gnomad4 ASJ exome AF: 0.0000493

Gnomad4 EAS exome AF: 0.00171

Gnomad4 SAS exome AF: 0.000119

Gnomad4 FIN exome AF: 0.00180

Gnomad4 NFE exome AF: 0.00218

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00320 AC: 460 AN: 143912 Hom.: 2 Cov.: 0 AF XY: 0.00296 AC XY: 207 AN XY: 69878

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.00254

Gnomad4 ASJ AF: 0.000297

Gnomad4 EAS AF: 0.00114

Gnomad4 SAS AF: 0.000882

Gnomad4 FIN AF: 0.00298

Gnomad4 NFE AF: 0.00481

Gnomad4 OTH AF: 0.00353

ClinVar

Not reported in ClinVar

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;