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GeneBe

1-230710048-A-G

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 (β˜…β˜…).

Frequency

Genomes: 𝑓 0.58 ( 27970 hom., cov: 33)
Exomes 𝑓: 0.55 ( 41270 hom. )

Consequence

AGT
NM_001384479 missense

Scores

18

Clinical Significance

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

Conservation

PhyloP100: 0.514

Links

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
AGTNM_001384479.1 linkuse as main transcriptc.776T>C p.Met259Thr missense_variant 2/5 ENST00000366667.6
AGTNM_001382817.3 linkuse as main transcriptc.776T>C p.Met259Thr missense_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGTENST00000366667.6 linkuse as main transcriptc.776T>C p.Met259Thr missense_variant 2/51 NM_001384479.1 P1

Frequencies

GnomAD3 genomes
AF:
0.578
AC:
87869
AN:
152062
Hom.:
27970
Cov.:
33
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 submitterclinical testingPreventionGenetics, PreventionGenetics-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeNov 01, 2022- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 13, 2018This 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 submitterclinical testingGenome-Nilou LabJul 14, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This 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 providedreference populationiDNA GenomicsOct 12, 2021- -
Preeclampsia, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJan 01, 2005- -
Hypertension, essential, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJan 01, 2005- -
Susceptibility to progression to renal failure in IgA nephropathy Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJan 01, 2005- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.054
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.54
Cadd
Benign
0.35
Dann
Benign
0.47
DEOGEN2
Benign
0.21
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0028
N
LIST_S2
Benign
0.10
T
MetaRNN
Benign
8.1e-7
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.7
N
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.26
T
PROVEAN
Benign
1.6
N
REVEL
Benign
0.16
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.024
MPC
0.054
ClinPred
0.0090
T
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 SpliceAI and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

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

Other links and lift over

dbSNP: rs699; hg19: chr1-230845794; COSMIC: COSV64184214; COSMIC: COSV64184214;