1-11748476-C-T

Variant summary

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

The NM_020350.5(AGTRAP):​c.230C>T​(p.Pro77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

AGTRAP
NM_020350.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.908
Variant links:
Genes affected
AGTRAP (HGNC:13539): (angiotensin II receptor associated protein) This gene encodes a transmembrane protein localized to the plasma membrane and perinuclear vesicular structures. The gene product interacts with the angiotensin II type I receptor and negatively regulates angiotensin II signaling. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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
AGTRAPNM_020350.5 linkc.230C>T p.Pro77Leu missense_variant Exon 4 of 5 ENST00000314340.10 NP_065083.3 Q6RW13-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGTRAPENST00000314340.10 linkc.230C>T p.Pro77Leu missense_variant Exon 4 of 5 1 NM_020350.5 ENSP00000319713.5 Q6RW13-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250772
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461482
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.230C>T (p.P77L) alteration is located in exon 4 (coding exon 4) of the AGTRAP gene. This alteration results from a C to T substitution at nucleotide position 230, causing the proline (P) at amino acid position 77 to be replaced by a leucine (L). 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
Benign
0.22
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
17
DANN
Benign
0.73
DEOGEN2
Benign
0.24
.;T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Benign
0.11
Sift
Benign
0.075
T;D
Sift4G
Benign
0.14
T;T
Polyphen
0.96
D;D
Vest4
0.68
MutPred
0.46
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
0.51
MPC
0.80
ClinPred
0.96
D
GERP RS
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.094
gMVP
0.87

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

LitVar

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

Other links and lift over

dbSNP: rs1259685768; hg19: chr1-11808533; API