NM_001384479.1:c.803C>T

Variant names:

• chr1-230710021-G-A
• rs1228544607
• NM_001384479.1:c.803C>T
• AGT p.Ala268Val

Germline classificationCancer classification (beta)

Variant summary

Our verdict is

Uncertain significance

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 0 ACMG points: 1P and 1B. O3_SupportingB3_Supporting

The NM_001384479.1(AGT):c.803C>T (p.Ala268Val) 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 0.00000684 (AC=10) in the gnomAD database across 1,461,848 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00000455. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.A268D: Uncertain_significance (ClinVar VariationId 2328349, 1 star)

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: AGT NM_001384479.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30
• Publications: 3 publications found

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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

Classification according to ACGS-UK Somatic Oncogenicity v2025

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• O3: Very rare in gnomAD (popmax AF <0.01%) — O3 supporting; GnomAD effective popmax AF = 0.000005 — very rare (O3 supporting [+1])
• B3: Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001384479.1	MANE Select	c.803C>T	p.Ala268Val	missense	Exon 2 of 5	NP_001371408.1	P01019
	AGT	NM_001382817.3		c.803C>T	p.Ala268Val	missense	Exon 2 of 5	NP_001369746.2	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.803C>T	p.Ala268Val	missense	Exon 2 of 5	ENSP00000355627.5	P01019
	AGT	ENST00000680041.1		c.803C>T	p.Ala268Val	missense	Exon 2 of 5	ENSP00000504866.1	P01019
	AGT	ENST00000681269.1		c.803C>T	p.Ala268Val	missense	Exon 2 of 5	ENSP00000505985.1	P01019

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251382 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.19
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Varity_R		0.10
gMVP		0.20
Mutation Taster		=83/17	polymorphism

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.

Other links and lift over

dbSNP: rs1228544607;

hg19: chr1-230845767;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar