chr10-50991310-AGCC-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 109 AD,Unknown gene.

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.-38_-36delGCC		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.-38_-36delGCC		5_prime_UTR	Exon 1 of 18	ENSP00000384200.4	Q13976-1

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

African (AFR) AF: 0.000505 AC: 11 AN: 21766

American (AMR) AF: 0.00214 AC: 50 AN: 23320

Ashkenazi Jewish (ASJ) AF: 0.000793 AC: 16 AN: 20170

East Asian (EAS) AF: 0.000525 AC: 15 AN: 28578

South Asian (SAS) AF: 0.00105 AC: 70 AN: 66522

European-Finnish (FIN) AF: 0.000680 AC: 30 AN: 44114

Middle Eastern (MID) AF: 0.000727 AC: 3 AN: 4124

European-Non Finnish (NFE) AF: 0.00109 AC: 1079 AN: 987502

Other (OTH) AF: 0.000979 AC: 50 AN: 51052

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

African (AFR) AF: 0.000457 AC: 18 AN: 39370

American (AMR) AF: 0.000494 AC: 7 AN: 14168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3366

East Asian (EAS) AF: 0.00 AC: 0 AN: 4384

South Asian (SAS) AF: 0.000220 AC: 1 AN: 4536

European-Finnish (FIN) AF: 0.000103 AC: 1 AN: 9738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000935 AC: 61 AN: 65216

Other (OTH) AF: 0.00101 AC: 2 AN: 1984

Alfa AF: 0.00 Hom.: 279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=300/0	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs79957958; hg19: chr10-52751070;