Variant chr10-51699238-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015235.3(CSTF2T):c.312T>C(p.Leu104Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,698 control chromosomes in the GnomAD database, including 31,158 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 0.27 ( 8388 hom., cov: 31)

Exomes 𝑓: 0.16 ( 22770 hom. )

Consequence

CSTF2T
NM_015235.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.15

Variant links:

Genes affected

CSTF2T (HGNC:17086): (cleavage stimulation factor subunit 2 tau variant) Enables RNA binding activity. Predicted to be involved in pre-mRNA cleavage required for polyadenylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CSTF2T links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-3.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSTF2T	NM_015235.3 linkuse as main transcript	c.312T>C	p.Leu104Leu	synonymous_variant	1/1	ENST00000331173.6	NP_056050.1	Q9H0L4
PRKG1	NM_006258.4 linkuse as main transcript	c.593-105347A>G		intron_variant		ENST00000373980.11	NP_006249.1	Q13976-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSTF2T	ENST00000331173.6 linkuse as main transcript	c.312T>C	p.Leu104Leu	synonymous_variant	1/1	6	NM_015235.3	ENSP00000332444.4		Q9H0L4
PRKG1	ENST00000373980.11 linkuse as main transcript	c.593-105347A>G		intron_variant		1	NM_006258.4	ENSP00000363092.5		Q13976-2

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41001

AN:

151698

Hom.:

8350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.235

GnomAD3 exomes

AF:

0.183

AC:

45987

AN:

251214

Hom.:

5753

AF XY:

0.178

AC XY:

24105

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.583

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.159

AC:

232571

AN:

1461882

Hom.:

22770

Cov.:

AF XY:

0.159

AC XY:

115863

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.595

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.271

AC:

41100

AN:

151816

Hom.:

8388

Cov.:

AF XY:

0.269

AC XY:

19983

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.581

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.204

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.182

Hom.:

2441

Bravo

AF:

0.279

Asia WGS

AF:

0.234

AC:

815

AN:

3478

EpiCase

AF:

0.134

EpiControl

AF:

0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.16

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over