1-230710021-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384479.1(AGT):​c.803C>A​(p.Ala268Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AGT
NM_001384479.1 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGTNM_001384479.1 linkc.803C>A p.Ala268Asp missense_variant Exon 2 of 5 ENST00000366667.6 NP_001371408.1
AGTNM_001382817.3 linkc.803C>A p.Ala268Asp missense_variant Exon 2 of 5 NP_001369746.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGTENST00000366667.6 linkc.803C>A p.Ala268Asp missense_variant Exon 2 of 5 1 NM_001384479.1 ENSP00000355627.5 P01019

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461848
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 12, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.830C>A (p.A277D) alteration is located in exon 2 (coding exon 1) of the AGT gene. This alteration results from a C to A substitution at nucleotide position 830, causing the alanine (A) at amino acid position 277 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
16
DANN
Benign
0.84
DEOGEN2
Pathogenic
0.81
D
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.081
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.10
B
Vest4
0.47
MutPred
0.75
Loss of catalytic residue at A277 (P = 0.1106);
MVP
0.68
MPC
0.12
ClinPred
0.30
T
GERP RS
1.3
Varity_R
0.84
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-230845767; API