rs10824310

Variant names:

• chr10-52268704-C-T
• rs10824310
• NM_006258.4:c.1174-2646C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKG1	NM_006258.4	c.1174-2646C>T		intron_variant	Intron 10 of 17	ENST00000373980.11	NP_006249.1
PRKG1	NM_001098512.3	c.1129-2646C>T		intron_variant	Intron 10 of 17		NP_001091982.1
PRKG1	NM_001374781.1	c.-36-2646C>T		intron_variant	Intron 6 of 13		NP_001361710.1
PRKG1	XM_017016413.2	c.871-2646C>T		intron_variant	Intron 10 of 17		XP_016871902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11	c.1174-2646C>T		intron_variant	Intron 10 of 17	1	NM_006258.4	ENSP00000363092.5

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

African (AFR) AF: 0.0338 AC: 1402 AN: 41502

American (AMR) AF: 0.0491 AC: 748 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3468

East Asian (EAS) AF: 0.0793 AC: 408 AN: 5142

South Asian (SAS) AF: 0.191 AC: 919 AN: 4820

European-Finnish (FIN) AF: 0.0468 AC: 495 AN: 10578

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0481 AC: 3266 AN: 67942

Other (OTH) AF: 0.0611 AC: 129 AN: 2110

Alfa AF: 0.0477 Hom.: 279

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
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10824310; hg19: chr10-54028464;