rs10824310

chr10-52268704-C-T

Variant summary

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

The NM_006258.4(PRKG1):c.1174-2646C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 151,998 control chromosomes in the GnomAD database, including 270 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 0.050 (270 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_006258.4	c.1174-2646C>T		intron_variant		ENST00000373980.11
PRKG1	NM_001098512.3	c.1129-2646C>T		intron_variant
PRKG1	NM_001374781.1	c.-36-2646C>T		intron_variant
PRKG1	XM_017016413.2	c.871-2646C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000373980.11	c.1174-2646C>T		intron_variant		1	NM_006258.4
PRKG1-AS1	ENST00000452247.7	n.461+25211G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7528 AN: 151880 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0560

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

GnomAD4 genome AF: 0.0497 AC: 7547 AN: 151998 Hom.: 270 Cov.: 32 AF XY: 0.0526 AC XY: 3905 AN XY: 74266

Gnomad4 AFR AF: 0.0338

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0793

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0468

Gnomad4 NFE AF: 0.0481

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0483 Hom.: 181

Bravo AF: 0.0441

Asia WGS AF: 0.167 AC: 579 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.4
Dann	Benign	0.34

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: rs10824310; hg19: chr10-54028464;