rs376174664

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006258.4(PRKG1):c.1963-16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,598,792 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

PRKG1
NM_006258.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.148

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:

PRKG1-AS1 (HGNC:45029): (PRKG1 antisense RNA 1)

PRKG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-52293786-T-G is Benign according to our data. Variant chr10-52293786-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 440195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-52293786-T-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_006258.4 link	c.1963-16T>G	intron_variant	Intron 17 of 17	ENST00000373980.11	NP_006249.1	Q13976-2
PRKG1	NM_001098512.3 link	c.1918-16T>G	intron_variant	Intron 17 of 17		NP_001091982.1	Q13976-1
PRKG1	NM_001374781.1 link	c.754-16T>G	intron_variant	Intron 13 of 13		NP_001361710.1
PRKG1	XM_017016413.2 link	c.1660-16T>G	intron_variant	Intron 17 of 17		XP_016871902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11 link	c.1963-16T>G		intron_variant	Intron 17 of 17	1	NM_006258.4	ENSP00000363092.5		Q13976-2

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000401

AC:

AN:

244148

Hom.:

AF XY:

0.000440

AC XY:

AN XY:

131932

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.000791

Gnomad OTH exome

AF:

0.000504

GnomAD4 exome

AF:

0.000805

AC:

1164

AN:

1446706

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

594

AN XY:

720092

show subpopulations

Gnomad4 AFR exome

AF:

0.000213

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000418

GnomAD4 genome

AF:

0.000506

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000470

Hom.:

Bravo

AF:

0.000423

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 20, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 11, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:2

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aortic aneurysm, familial thoracic 8

Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder

Benign:1

Jun 01, 2018

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.22

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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