rs10508958

chr10-51828280-A-Cchr10-51828280-A-Gchr10-51828280-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006258.4(PRKG1):c.698+23590A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,882 control chromosomes in the GnomAD database, including 18,304 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (18304 hom., cov: 31)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_006258.4	c.698+23590A>C		intron_variant		ENST00000373980.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000373980.11	c.698+23590A>C		intron_variant		1	NM_006258.4

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69237 AN: 151764 Hom.: 18310 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 69234 AN: 151882 Hom.: 18304 Cov.: 31 AF XY: 0.457 AC XY: 33881 AN XY: 74186

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.477

Alfa AF: 0.539 Hom.: 9370

Bravo AF: 0.434

Asia WGS AF: 0.430 AC: 1491 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.67
Dann	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs10508958; hg19: chr10-53588040; COSMIC: COSV64794020;