chr10-50991310-AGCCGCCGCC-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001098512.3(PRKG1):​c.-44_-36delGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,395,442 control chromosomes in the GnomAD database, including 41,943 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3021 hom., cov: 0)
  • Exomes 𝑓: 0.25 (38922 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.62
• Publications: 3 publications found

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]

PRKG1 Gene-Disease associations (from GenCC):

• aortic aneurysm, familial thoracic 8

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-50991310-AGCCGCCGCC-A is Benign according to our data. Variant chr10-50991310-AGCCGCCGCC-A is described in ClinVar as Benign. ClinVar VariationId is 1221009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098512.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	NM_001098512.3		c.-44_-36delGCCGCCGCC		5_prime_UTR	Exon 1 of 18	NP_001091982.1	Q13976-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000401604.8	TSL:5	c.-44_-36delGCCGCCGCC		5_prime_UTR	Exon 1 of 18	ENSP00000384200.4	Q13976-1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 27206 AN: 143720 Hom.: 3019 Cov.: 0

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.252 AC: 315664 AN: 1251624 Hom.: 38922 AF XY: 0.253 AC XY: 156220 AN XY: 616680

African (AFR) AF: 0.0514 AC: 1120 AN: 21796

American (AMR) AF: 0.336 AC: 7887 AN: 23462

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 5831 AN: 20254

East Asian (EAS) AF: 0.115 AC: 3294 AN: 28630

South Asian (SAS) AF: 0.318 AC: 21374 AN: 67196

European-Finnish (FIN) AF: 0.275 AC: 12169 AN: 44292

Middle Eastern (MID) AF: 0.251 AC: 1044 AN: 4152

European-Non Finnish (NFE) AF: 0.253 AC: 250736 AN: 990596

Other (OTH) AF: 0.238 AC: 12209 AN: 51246

GnomAD4 genome AF: 0.189 AC: 27213 AN: 143818 Hom.: 3021 Cov.: 0 AF XY: 0.195 AC XY: 13631 AN XY: 69830

African (AFR) AF: 0.0457 AC: 1798 AN: 39358

American (AMR) AF: 0.248 AC: 3506 AN: 14142

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 968 AN: 3364

East Asian (EAS) AF: 0.119 AC: 521 AN: 4382

South Asian (SAS) AF: 0.312 AC: 1416 AN: 4534

European-Finnish (FIN) AF: 0.279 AC: 2713 AN: 9726

Middle Eastern (MID) AF: 0.208 AC: 59 AN: 284

European-Non Finnish (NFE) AF: 0.240 AC: 15654 AN: 65180

Other (OTH) AF: 0.213 AC: 422 AN: 1982

Alfa AF: 0.165 Hom.: 279

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79957958; hg19: chr10-52751070; COSMIC: COSV64880060;