AGT M259T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001384479(AGT):c.776T>C(p.Met259Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152062 control chromosomes in the gnomAD Genomes database, including 27970 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27970 hom., cov: 33)

Exomes 𝑓: 0.55 ( 41270 hom. )

Consequence

AGT
NM_001384479 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:3

Conservation

PhyloP100: 0.514

Links

AGT (HGNC:333):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.121765E-7).

BP6

Variant 1:230710048-A>G is Benign according to our data. Variant chr1-230710048-A-G is described in ClinVar as [Benign]. Clinvar id is 18068. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-230710048-A-G is described in Lovd as [Benign].

BA1

GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1 linkuse as main transcript	c.776T>C	p.Met259Thr	missense_variant	2/5	ENST00000366667.6
AGT	NM_001382817.3 linkuse as main transcript	c.776T>C	p.Met259Thr	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6 linkuse as main transcript	c.776T>C	p.Met259Thr	missense_variant	2/5	1	NM_001384479.1	P1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87869

AN:

152062

Hom.:

27970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.631

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.548

GnomAD3 exomes

AF:

0.548

AC:

137772

AN:

251344

Hom.:

41270

AF XY:

0.536

AC XY:

72890

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.845

Gnomad AMR exome

AF:

0.720

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.839

Gnomad SAS exome

AF:

0.620

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.458

AC:

669469

AN:

1461692

Hom.:

163148

AF XY:

0.462

AC XY:

335636

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.847

Gnomad4 AMR exome

AF:

0.709

Gnomad4 ASJ exome

AF:

0.434

Gnomad4 EAS exome

AF:

0.825

Gnomad4 SAS exome

AF:

0.615

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.497

Alfa

AF:

0.455

Hom.:

41273

Bravo

AF:

0.604

TwinsUK

AF:

0.411

AC:

1525

ALSPAC

AF:

0.395

AC:

1524

ESP6500AA

AF:

0.827

AC:

3643

ESP6500EA

AF:

0.426

AC:

3662

ExAC

AF:

0.548

AC:

66560

Asia WGS

AF:

0.729

AC:

2532

AN:

3478

EpiCase

AF:

0.426

EpiControl

AF:

0.424

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, PreventionGenetics	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 01, 2022	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 13, 2018	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. -

Renal tubular dysgenesis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hypertensive disorder

Benign:1

Benign, no assertion criteria provided

reference population

iDNA Genomics

Oct 12, 2021

- -

Preeclampsia, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jan 01, 2005

- -

Hypertension, essential, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jan 01, 2005

- -

Susceptibility to progression to renal failure in IgA nephropathy

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jan 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

Cadd

Benign

0.35

Dann

Benign

0.47

DEOGEN2

Benign

0.21

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.10

MetaRNN

Benign

8.1e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

1.6

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.024

MPC

0.054

ClinPred

0.0090

GERP RS

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.14

Splicing

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over