rs387906578
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The ENST00000366667.6(AGT):c.1263delT(p.Phe421LeufsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
AGT
ENST00000366667.6 frameshift
ENST00000366667.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0570
Publications
9 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 originInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.117 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-230703308-CA-C is Pathogenic according to our data. Variant chr1-230703308-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 18072.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000366667.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AGT | NM_001384479.1 | MANE Select | c.1263delT | p.Phe421LeufsTer25 | frameshift | Exon 5 of 5 | NP_001371408.1 | ||
| AGT | NM_001382817.3 | c.1263delT | p.Phe421LeufsTer25 | frameshift | Exon 5 of 5 | NP_001369746.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AGT | ENST00000366667.6 | TSL:1 MANE Select | c.1263delT | p.Phe421LeufsTer25 | frameshift | Exon 5 of 5 | ENSP00000355627.5 | ||
| AGT | ENST00000680041.1 | c.1263delT | p.Phe421LeufsTer25 | frameshift | Exon 5 of 5 | ENSP00000504866.1 | |||
| AGT | ENST00000681269.1 | c.1263delT | p.Phe421LeufsTer25 | frameshift | Exon 5 of 5 | ENSP00000505985.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00 AC: 0AN: 250386 AF XY: 0.00
GnomAD2 exomes
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461642Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727140 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461642
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727140
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
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0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
1
AN:
86242
European-Finnish (FIN)
AF:
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111832
Other (OTH)
AF:
AC:
0
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
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ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Renal tubular dysgenesis (1)
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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