rs4762

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025): 0P and 4B. B1_Strong

The NM_001384479.1(AGT):c.593C>T (p.Thr198Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene AGT is a tumor suppressor gene (CancerMine: 1 TSG, 1 oncogene, 1 driver citations). The gene AGT is a known oncogene (CancerMine: 1 TSG, 1 oncogene, 1 driver citations). The gene AGT is a cancer driver gene (CancerMine: 1 TSG, 1 oncogene, 1 driver citations). The variant allele was found at a cumulative frequency of 0.122 (AC=196,109) in the gnomAD database across 1,613,596 control chromosomes, including 12,433 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.126. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.T198= (synonymous): Conflicting_classifications_of_pathogenicity (ClinVar VariationId 2176272) The variant has been observed in cBioPortal in 4 samples across 4 studies and 3 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.). This exact variant is curated in the UniProt human variants database as Uncertain Significance.

Frequency

Genomes: 𝑓 0.11 ( 1080 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11353 hom. )

Consequence

AGT
NM_001384479.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.38

Publications

353 publications found

Variant links:

Genes affected

AGT (HGNC:333): (angiotensinogen) The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

AGT Gene-Disease associations (from GenCC):

renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

AGT links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001384479.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

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

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.126 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001384479.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001384479.1	MANE Select	c.593C>T	p.Thr198Met	missense	Exon 2 of 5	NP_001371408.1	P01019
	AGT	NM_001382817.3		c.593C>T	p.Thr198Met	missense	Exon 2 of 5	NP_001369746.2	P01019

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGT	ENST00000366667.6	TSL:1 MANE Select	c.593C>T	p.Thr198Met	missense	Exon 2 of 5	ENSP00000355627.5	P01019
AGT	ENST00000680041.1		c.593C>T	p.Thr198Met	missense	Exon 2 of 5	ENSP00000504866.1	P01019
AGT	ENST00000681269.1		c.593C>T	p.Thr198Met	missense	Exon 2 of 5	ENSP00000505985.1	P01019

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17040

AN:

152154

Hom.:

1082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0647

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.124

AC:

31006

AN:

249646

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.0618

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.123

AC:

179076

AN:

1461324

Hom.:

11353

Cov.:

AF XY:

0.123

AC XY:

89491

AN XY:

726958

show subpopulations

African (AFR)

AF:

0.0612

AC:

2049

AN:

33480

American (AMR)

AF:

0.122

AC:

5463

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

3601

AN:

26136

East Asian (EAS)

AF:

0.104

AC:

4133

AN:

39700

South Asian (SAS)

AF:

0.128

AC:

11075

AN:

86258

European-Finnish (FIN)

AF:

0.173

AC:

9140

AN:

52890

Middle Eastern (MID)

AF:

0.112

AC:

644

AN:

5768

European-Non Finnish (NFE)

AF:

0.122

AC:

135939

AN:

1111986

Other (OTH)

AF:

0.116

AC:

7032

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

12149

24298

36447

48596

60745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4856

9712

14568

19424

24280

<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:

0.112

AC:

17033

AN:

152272

Hom.:

1080

Cov.:

AF XY:

0.115

AC XY:

8532

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0645

AC:

2681

AN:

41568

American (AMR)

AF:

0.111

AC:

1706

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

490

AN:

3472

East Asian (EAS)

AF:

0.105

AC:

544

AN:

5174

South Asian (SAS)

AF:

0.129

AC:

623

AN:

4822

European-Finnish (FIN)

AF:

0.193

AC:

2053

AN:

10614

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8488

AN:

67996

Other (OTH)

AF:

0.104

AC:

219

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

801

1601

2402

3202

4003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.118

Hom.:

3379

Bravo

AF:

0.103

Asia WGS

AF:

0.0990

AC:

342

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.121

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.106

AC:

13018

AN:

122718

Turkish Variome

AF:

0.141

AC:

874

AN:

6180

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.101

AC:

908

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.105

AC:

246

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Renal tubular dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.8

PhyloP100

2.4

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.32

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.012

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.48

Mutation Taster

=88/12

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over