chr10-50991310-AGCC-A

Variant names:

• chr10-50991310-AGCC-A
• rs79957958
• NM_001098512.3:c.-38_-36delGCC

Variant summary

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

The NM_001098512.3(PRKG1):​c.-38_-36delGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,391,062 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (6 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 109 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_001098512.3	c.-38_-36delGCC		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.-38_-36delGCC		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000384200.4

Frequencies

GnomAD3 genomes AF: 0.000751 AC: 108 AN: 143816 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000433

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.000495

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000935

Gnomad OTH AF: 0.00102

GnomAD4 exome AF: 0.00106 AC: 1324 AN: 1247148 Hom.: 6 AF XY: 0.00105 AC XY: 644 AN XY: 614478

Gnomad4 AFR exome AF: 0.000505

Gnomad4 AMR exome AF: 0.00214

Gnomad4 ASJ exome AF: 0.000793

Gnomad4 EAS exome AF: 0.000525

Gnomad4 SAS exome AF: 0.00105

Gnomad4 FIN exome AF: 0.000680

Gnomad4 NFE exome AF: 0.00109

Gnomad4 OTH exome AF: 0.000979

GnomAD4 genome AF: 0.000757 AC: 109 AN: 143914 Hom.: 0 Cov.: 0 AF XY: 0.000758 AC XY: 53 AN XY: 69880

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.000494

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000220

Gnomad4 FIN AF: 0.000103

Gnomad4 NFE AF: 0.000935

Gnomad4 OTH AF: 0.00101

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;