chr10-52271683-T-C

Variant names:

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

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.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
• Publications: 3 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=-0.78).
• BP6: Variant 10-52271683-T-C is Benign according to our data. Variant chr10-52271683-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006258.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	NM_006258.4	MANE Select	c.1313+194T>C		intron	N/A	NP_006249.1
	PRKG1	NM_001098512.3		c.1268+194T>C		intron	N/A	NP_001091982.1
	PRKG1	NM_001374781.1		c.104+194T>C		intron	N/A	NP_001361710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.1313+194T>C		intron	N/A	ENSP00000363092.5
	PRKG1-AS1	ENST00000426785.2	TSL:1	n.170-18243A>G		intron	N/A
	PRKG1	ENST00000401604.8	TSL:5	c.1268+194T>C		intron	N/A	ENSP00000384200.4

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

African (AFR) AF: 0.788 AC: 32681 AN: 41484

American (AMR) AF: 0.925 AC: 14112 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3053 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5163 AN: 5166

South Asian (SAS) AF: 0.938 AC: 4523 AN: 4820

European-Finnish (FIN) AF: 0.984 AC: 10448 AN: 10620

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.944 AC: 64201 AN: 68004

Other (OTH) AF: 0.902 AC: 1905 AN: 2112

Alfa AF: 0.928 Hom.: 108749

Bravo AF: 0.893

Asia WGS AF: 0.965 AC: 3351 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.87
PhyloP100		-0.011
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: rs1194516; hg19: chr10-54031443;