10-50991310-A-AGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001098512.3(PRKG1):c.-38_-36dup 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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3	c.-38_-36dup		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8	c.-38_-36dup		5_prime_UTR_variant	1/18	5		P1

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

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.286

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

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.351

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 19, 2019

- -

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;