rs202146491

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015235.3(CSTF2T):c.1624G>A(p.Gly542Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000482 in 1,599,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

CSTF2T
NM_015235.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.731

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

aortic aneurysm, familial thoracic 8
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen

PRKG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018237919).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015235.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSTF2T	NM_015235.3	MANE Select	c.1624G>A	p.Gly542Ser	missense	Exon 1 of 1	NP_056050.1	Q9H0L4
PRKG1	NM_006258.4	MANE Select	c.593-106659C>T		intron	N/A	NP_006249.1	Q13976-2
PRKG1	NM_001098512.3		c.548-106659C>T		intron	N/A	NP_001091982.1	Q13976-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSTF2T	ENST00000331173.6	TSL:6 MANE Select	c.1624G>A	p.Gly542Ser	missense	Exon 1 of 1	ENSP00000332444.4	Q9H0L4
PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.593-106659C>T		intron	N/A	ENSP00000363092.5	Q13976-2
PRKG1	ENST00000401604.8	TSL:5	c.548-106659C>T		intron	N/A	ENSP00000384200.4	Q13976-1

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

151496

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000537

AC:

AN:

223544

AF XY:

0.0000498

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000196

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000628

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000404

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000463

AC:

AN:

1447538

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

719018

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000609

AC:

AN:

32842

American (AMR)

AF:

0.000216

AC:

AN:

41736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25906

East Asian (EAS)

AF:

0.0000517

AC:

AN:

38686

South Asian (SAS)

AF:

0.0000235

AC:

AN:

84948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52762

Middle Eastern (MID)

AF:

0.000869

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000371

AC:

AN:

1104966

Other (OTH)

AF:

0.000100

AC:

AN:

59936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.349

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000660

AC:

AN:

151614

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.0000972

AC:

AN:

41158

American (AMR)

AF:

0.000131

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5072

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.0000495

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.6

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.062

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.51

M_CAP

Benign

0.0070

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PhyloP100

0.73

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.15

REVEL

Benign

0.024

Sift

Benign

0.066

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.28

MVP

0.18

MPC

0.23

ClinPred

0.024

GERP RS

1.4

Varity_R

0.11

gMVP

0.67

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over