10-50991310-AGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCC

Variant names:

• chr10-50991310-AGCCGCC-A
• rs79957958
• NM_001098512.3:c.-41_-36delGCCGCC

Variant summary

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

The NM_001098512.3(PRKG1):​c.-41_-36delGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000677 in 1,396,968 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00059 (8 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 207 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_001098512.3	c.-41_-36delGCCGCC		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.-41_-36delGCCGCC		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000384200.4

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 207 AN: 143816 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.000594

Gnomad EAS AF: 0.000909

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.000767

Gnomad OTH AF: 0.00306

GnomAD4 exome AF: 0.000590 AC: 739 AN: 1253054 Hom.: 8 AF XY: 0.000562 AC XY: 347 AN XY: 617556

Gnomad4 AFR exome AF: 0.00271

Gnomad4 AMR exome AF: 0.000808

Gnomad4 ASJ exome AF: 0.0000493

Gnomad4 EAS exome AF: 0.000698

Gnomad4 SAS exome AF: 0.000713

Gnomad4 FIN exome AF: 0.000495

Gnomad4 NFE exome AF: 0.000522

Gnomad4 OTH exome AF: 0.000974

GnomAD4 genome AF: 0.00144 AC: 207 AN: 143914 Hom.: 0 Cov.: 0 AF XY: 0.00146 AC XY: 102 AN XY: 69878

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.000594

Gnomad4 EAS AF: 0.000912

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000103

Gnomad4 NFE AF: 0.000767

Gnomad4 OTH AF: 0.00303

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;