rs1228544607

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_001384479.1(AGT):c.803C>A (p.Ala268Asp) 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 0.000000684 (AC=1) in the gnomAD database across 1,461,848 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000000899. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

Publications

0 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, Labcorp Genetics (formerly Invitae), PanelApp Australia

AGT links:

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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: Uncertain_significance. The variant received 2 points.

Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = 0.000001, AC = 1 — absent/extremely rare (O3 moderate [+2])

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.803C>A	p.Ala268Asp	missense	Exon 2 of 5	NP_001371408.1	P01019
	AGT	NM_001382817.3		c.803C>A	p.Ala268Asp	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.803C>A	p.Ala268Asp	missense	Exon 2 of 5	ENSP00000355627.5	P01019
AGT	ENST00000680041.1		c.803C>A	p.Ala268Asp	missense	Exon 2 of 5	ENSP00000504866.1	P01019
AGT	ENST00000681269.1		c.803C>A	p.Ala268Asp	missense	Exon 2 of 5	ENSP00000505985.1	P01019

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes					32
GnomAD4 exome	6.84e-7	1	0	1461848	32
GnomAD4 genome					32

Showing 3 sources

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Pathogenic	-	20
AlphaMissense	Uncertain	-	0.43
BayesDel_addAF	Uncertain	T	0.054
BayesDel_noAF	Benign	-	-0.16
CADD	Benign	-	16
DANN	Benign	-	0.84
DEOGEN2	Pathogenic	D	0.81
Eigen	Benign	-	-1.0
Eigen_PC	Benign	-	-0.95
FATHMM_MKL	Benign	N	0.28
FuncVEP CTI	Benign	-	0.38
GPN-Star LLR	N/A	-	0.29
GPN-Star score	N/A	-	-0.29
LIST_S2	Benign	T	0.55
M_CAP	Benign	D	0.081
MetaRNN	Uncertain	D	0.74
MetaSVM	Benign	T	-0.72
Mutation Taster	N/A	polymorphism	84/16
MutationAssessor	Benign	N	0.0
PhyloP100	Uncertain	-	4.3
popEVE	Benign	-	-2.9
PrimateAI	Benign	T	0.27
PROVEAN	Uncertain	D	-2.8
REVEL	Uncertain	-	0.46
Sift	Uncertain	D	0.0010
Sift4G	Uncertain	D	0.0020
Varity_R	N/A	-	0.84
VESM-3B	Benign	-	-10

Showing 28 of 28 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

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

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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

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over