10-52272197-C-T

Variant names:

• chr10-52272197-C-T
• rs16928725
• NM_006258.4:c.1314-195C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006258.4(PRKG1):​c.1314-195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 151,986 control chromosomes in the GnomAD database, including 582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.076 (582 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.844
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-52272197-C-T is Benign according to our data. Variant chr10-52272197-C-T is described in ClinVar as Benign. ClinVar VariationId is 1297344.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.1314-195C>T		intron_variant	Intron 11 of 17	ENST00000373980.11	NP_006249.1
PRKG1	NM_001098512.3	c.1269-195C>T		intron_variant	Intron 11 of 17		NP_001091982.1
PRKG1	NM_001374781.1	c.105-195C>T		intron_variant	Intron 7 of 13		NP_001361710.1
PRKG1	XM_017016413.2	c.1011-195C>T		intron_variant	Intron 11 of 17		XP_016871902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11	c.1314-195C>T		intron_variant	Intron 11 of 17	1	NM_006258.4	ENSP00000363092.5

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11564 AN: 151868 Hom.: 575 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.0813

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0763 AC: 11590 AN: 151986 Hom.: 582 Cov.: 32 AF XY: 0.0785 AC XY: 5829 AN XY: 74284

African (AFR) AF: 0.126 AC: 5206 AN: 41472

American (AMR) AF: 0.0571 AC: 868 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3464

East Asian (EAS) AF: 0.0808 AC: 417 AN: 5164

South Asian (SAS) AF: 0.190 AC: 916 AN: 4816

European-Finnish (FIN) AF: 0.0474 AC: 502 AN: 10584

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3309 AN: 67964

Other (OTH) AF: 0.0776 AC: 164 AN: 2114

Alfa AF: 0.0598 Hom.: 513

Bravo AF: 0.0748

Asia WGS AF: 0.174 AC: 605 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.84
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: rs16928725; hg19: chr10-54031957;