10-50990905-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098512.3(PRKG1):c.-474C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (56051 hom., cov: 17)
  • Exomes 𝑓: 0.81 (357 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.386

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 10-50990905-C-T is Benign according to our data. Variant chr10-50990905-C-T is described in ClinVar as [Benign]. Clinvar id is 683714.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3	c.-474C>T		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8	c.-474C>T		5_prime_UTR_variant	1/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 124584 AN: 138804 Hom.: 55999 Cov.: 17

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.847

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.811 AC: 863 AN: 1064 Hom.: 357 Cov.: 0 AF XY: 0.819 AC XY: 480 AN XY: 586

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.789

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.818

Gnomad4 OTH exome AF: 0.787

GnomAD4 genome AF: 0.898 AC: 124688 AN: 138912 Hom.: 56051 Cov.: 17 AF XY: 0.896 AC XY: 59829 AN XY: 66756

Gnomad4 AFR AF: 0.952

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.884

Alfa AF: 0.884 Hom.: 6930

Bravo AF: 0.903

Asia WGS AF: 0.909 AC: 3163 AN: 3478

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

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	11
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2248908; hg19: chr10-52750665;