chr10-50991310-A-AGCC

Variant names:

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

Variant summary

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

The NM_001098512.3(PRKG1):​c.-38_-36dupGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13583 hom., cov: 0)
  • Exomes 𝑓: 0.27 (31338 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42
• 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-A-AGCC is Benign according to our data. Variant chr10-50991310-A-AGCC is described in ClinVar as Benign. ClinVar VariationId is 1296349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 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.-38_-36dupGCC		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_-36dupGCC		5_prime_UTR	Exon 1 of 18	ENSP00000384200.4	Q13976-1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 58402 AN: 143552 Hom.: 13558 Cov.: 0

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.268 AC: 331786 AN: 1240052 Hom.: 31338 Cov.: 13 AF XY: 0.267 AC XY: 162969 AN XY: 611178

African (AFR) AF: 0.571 AC: 12325 AN: 21568

American (AMR) AF: 0.185 AC: 4212 AN: 22800

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 5411 AN: 20012

East Asian (EAS) AF: 0.303 AC: 8624 AN: 28474

South Asian (SAS) AF: 0.223 AC: 14716 AN: 66064

European-Finnish (FIN) AF: 0.228 AC: 10109 AN: 44254

Middle Eastern (MID) AF: 0.267 AC: 1097 AN: 4114

European-Non Finnish (NFE) AF: 0.266 AC: 260752 AN: 981956

Other (OTH) AF: 0.286 AC: 14540 AN: 50810

GnomAD4 genome AF: 0.407 AC: 58471 AN: 143648 Hom.: 13583 Cov.: 0 AF XY: 0.399 AC XY: 27837 AN XY: 69766

African (AFR) AF: 0.680 AC: 26717 AN: 39284

American (AMR) AF: 0.299 AC: 4234 AN: 14140

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1033 AN: 3364

East Asian (EAS) AF: 0.381 AC: 1669 AN: 4376

South Asian (SAS) AF: 0.270 AC: 1224 AN: 4528

European-Finnish (FIN) AF: 0.248 AC: 2410 AN: 9712

Middle Eastern (MID) AF: 0.356 AC: 101 AN: 284

European-Non Finnish (NFE) AF: 0.309 AC: 20114 AN: 65114

Other (OTH) AF: 0.351 AC: 695 AN: 1978

Alfa AF: 0.246 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		2.4
Mutation Taster		=300/0	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;