NM_001098512.3:c.-47_-36delGCCGCCGCCGCC

Variant names:

• chr10-50991310-AGCCGCCGCCGCC-A
• rs79957958
• NM_001098512.3:c.-47_-36delGCCGCCGCCGCC

Variant summary

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

The NM_001098512.3(PRKG1):​c.-47_-36delGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,391,400 control chromosomes in the GnomAD database, including 23 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0032 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 465 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_001098512.3	c.-47_-36delGCCGCCGCCGCC		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.-47_-36delGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000384200.4

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 466 AN: 143810 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00907

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00212

Gnomad ASJ AF: 0.00535

Gnomad EAS AF: 0.000227

Gnomad SAS AF: 0.000661

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0196

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.00255

GnomAD4 exome AF: 0.00110 AC: 1370 AN: 1247492 Hom.: 23 AF XY: 0.00104 AC XY: 637 AN XY: 614694

Gnomad4 AFR exome AF: 0.0109

Gnomad4 AMR exome AF: 0.00486

Gnomad4 ASJ exome AF: 0.00458

Gnomad4 EAS exome AF: 0.000245

Gnomad4 SAS exome AF: 0.000360

Gnomad4 FIN exome AF: 0.000204

Gnomad4 NFE exome AF: 0.000772

Gnomad4 OTH exome AF: 0.00206

GnomAD4 genome AF: 0.00323 AC: 465 AN: 143908 Hom.: 0 Cov.: 0 AF XY: 0.00286 AC XY: 200 AN XY: 69870

Gnomad4 AFR AF: 0.00904

Gnomad4 AMR AF: 0.00212

Gnomad4 ASJ AF: 0.00535

Gnomad4 EAS AF: 0.000228

Gnomad4 SAS AF: 0.000661

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000705

Gnomad4 OTH AF: 0.00252

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;