Variant chr10-50990905-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.386

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.-474C>T		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8 linkuse as main transcript	c.-474C>T		5_prime_UTR_variant	1/18	5		P1	Q13976-1

Frequencies

GnomAD3 genomes

AF:

0.898

AC:

124584

AN:

138804

Hom.:

55999

Cov.:

show subpopulations

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.:

AF XY:

0.819

AC XY:

480

AN XY:

586

show subpopulations

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.:

AF XY:

0.896

AC XY:

59829

AN XY:

66756

show subpopulations

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

LINK: link

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

DANN

Benign

0.67

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over