10-52271683-T-C

Variant names:

• chr10-52271683-T-C
• rs1194516
• NM_006258.4:c.1313+194T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006258.4(PRKG1):​c.1313+194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,140 control chromosomes in the GnomAD database, including 62,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.90 (62279 hom., cov: 33)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-52271683-T-C is Benign according to our data. Variant chr10-52271683-T-C is described in ClinVar as [Benign]. Clinvar id is 674715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_006258.4	c.1313+194T>C		intron_variant	Intron 11 of 17	ENST00000373980.11	NP_006249.1
PRKG1	NM_001098512.3	c.1268+194T>C		intron_variant	Intron 11 of 17		NP_001091982.1
PRKG1	NM_001374781.1	c.104+194T>C		intron_variant	Intron 7 of 13		NP_001361710.1
PRKG1	XM_017016413.2	c.1010+194T>C		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.1313+194T>C		intron_variant	Intron 11 of 17	1	NM_006258.4	ENSP00000363092.5

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137084 AN: 152022 Hom.: 62236 Cov.: 33

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.902 AC: 137182 AN: 152140 Hom.: 62279 Cov.: 33 AF XY: 0.905 AC XY: 67340 AN XY: 74374

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.925

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.944

Gnomad4 OTH AF: 0.902

Alfa AF: 0.933 Hom.: 86662

Bravo AF: 0.893

Asia WGS AF: 0.965 AC: 3351 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.87

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: rs1194516; hg19: chr10-54031443;