10-50991310-AGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC

Variant names:

• chr10-50991310-A-AGCCGCCGCCGCCGCCGCCGCC
• rs79957958
• NM_001098512.3:c.-56_-36dupGCCGCCGCCGCCGCCGCCGCC

Variant summary

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

The NM_001098512.3(PRKG1):​c.-56_-36dupGCCGCCGCCGCCGCCGCCGCC 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 0.00014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000030 (0 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 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_001098512.3	c.-56_-36dupGCCGCCGCCGCCGCCGCCGCC		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.-56_-36dupGCCGCCGCCGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000384200.4

Frequencies

GnomAD3 genomes AF: 0.000139 AC: 20 AN: 143820 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000565

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000227

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000138

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000295 AC: 37 AN: 1253104 Hom.: 0 Cov.: 13 AF XY: 0.0000291 AC XY: 18 AN XY: 617576

Gnomad4 AFR exome AF: 0.0000459

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000349

Gnomad4 SAS exome AF: 0.0000149

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000303

Gnomad4 OTH exome AF: 0.0000780

GnomAD4 genome AF: 0.000139 AC: 20 AN: 143918 Hom.: 0 Cov.: 0 AF XY: 0.000143 AC XY: 10 AN XY: 69880

Gnomad4 AFR AF: 0.0000508

Gnomad4 AMR AF: 0.000565

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000228

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000138

Gnomad4 OTH AF: 0.00

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;