10-52014152-T-G

Position:

• chr10-52014152-T-G

Variant summary

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

The NM_006258.4(PRKG1):​c.763-40332T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,972 control chromosomes in the GnomAD database, including 14,873 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 0.43 (14873 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_006258.4	c.763-40332T>G		intron_variant		ENST00000373980.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000373980.11	c.763-40332T>G		intron_variant		1	NM_006258.4
PRKG1	ENST00000373976.9	c.763-40332T>G		intron_variant		3
PRKG1	ENST00000401604.8	c.718-40332T>G		intron_variant		5		P1
PRKG1	ENST00000645324.1	c.763-40332T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64783 AN: 151854 Hom.: 14863 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.426 AC: 64811 AN: 151972 Hom.: 14873 Cov.: 32 AF XY: 0.431 AC XY: 31987 AN XY: 74276

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.432

Alfa AF: 0.444 Hom.: 6898

Bravo AF: 0.428

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.52

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: rs10762524; hg19: chr10-53773912;