NM_001098512.3:c.-44_-36dupGCCGCCGCC

Variant names:

• chr10-50991310-A-AGCCGCCGCC
• rs79957958
• NM_001098512.3:c.-44_-36dupGCCGCCGCC

Variant summary

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

The NM_001098512.3(PRKG1):​c.-44_-36dupGCCGCCGCC 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 0.0025 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (9 hom.)
• 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 360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_001098512.3	c.-44_-36dupGCCGCCGCC		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.-44_-36dupGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000384200.4

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 350 AN: 143816 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00864

Gnomad SAS AF: 0.000661

Gnomad FIN AF: 0.000411

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000506

Gnomad OTH AF: 0.00255

GnomAD4 exome AF: 0.00112 AC: 1403 AN: 1251742 Hom.: 9 Cov.: 13 AF XY: 0.00105 AC XY: 648 AN XY: 616922

Gnomad4 AFR exome AF: 0.00666

Gnomad4 AMR exome AF: 0.000851

Gnomad4 ASJ exome AF: 0.000740

Gnomad4 EAS exome AF: 0.00740

Gnomad4 SAS exome AF: 0.000372

Gnomad4 FIN exome AF: 0.000564

Gnomad4 NFE exome AF: 0.000892

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.00250 AC: 360 AN: 143914 Hom.: 2 Cov.: 0 AF XY: 0.00240 AC XY: 168 AN XY: 69878

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.00162

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00867

Gnomad4 SAS AF: 0.000661

Gnomad4 FIN AF: 0.000411

Gnomad4 NFE AF: 0.000506

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;