10-51029595-T-C

Position:

• chr10-51029595-T-C

Variant summary

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

The NM_001098512.3(PRKG1):​c.266+37951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,158 control chromosomes in the GnomAD database, including 58,890 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 0.88 (58890 hom., cov: 32)
• Consequence: PRKG1 NM_001098512.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3	c.266+37951T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8	c.266+37951T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133652 AN: 152040 Hom.: 58843 Cov.: 32

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.879 AC: 133756 AN: 152158 Hom.: 58890 Cov.: 32 AF XY: 0.877 AC XY: 65248 AN XY: 74378

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.928

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.877

Alfa AF: 0.866 Hom.: 27835

Bravo AF: 0.886

Asia WGS AF: 0.893 AC: 3105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.6
DANN	Benign	0.64

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: rs6479874; hg19: chr10-52789355;