1-11747519-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020350.5(AGTRAP):​c.142C>T​(p.Arg48Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R48Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

AGTRAP
NM_020350.5 missense

Scores

2
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.651
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09681174).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGTRAPNM_020350.5 linkc.142C>T p.Arg48Trp missense_variant Exon 3 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.142C>T p.Arg48Trp missense_variant Exon 3 of 5 1 NM_020350.5 ENSP00000319713.5 Q6RW13-1

Frequencies

GnomAD3 genomes
AF:
0.000401
AC:
61
AN:
152170
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000955
AC:
24
AN:
251242
Hom.:
0
AF XY:
0.000110
AC XY:
15
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.00129
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS 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:
0.0000342
AC:
50
AN:
1461756
Hom.:
0
Cov.:
31
AF XY:
0.0000371
AC XY:
27
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000401
AC:
61
AN:
152288
Hom.:
0
Cov.:
33
AF XY:
0.000376
AC XY:
28
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.00144
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000750
Hom.:
0
Bravo
AF:
0.000408
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 13, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.142C>T (p.R48W) alteration is located in exon 3 (coding exon 3) of the AGTRAP gene. This alteration results from a C to T substitution at nucleotide position 142, causing the arginine (R) at amino acid position 48 to be replaced by a tryptophan (W). 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
0.26
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
.;.;T;.
Eigen
Benign
0.14
Eigen_PC
Benign
0.029
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.61
T;T;T;T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.097
T;T;T;T
MetaSVM
Benign
-0.37
T
PROVEAN
Benign
-2.0
N;D;N;D
REVEL
Benign
0.087
Sift
Pathogenic
0.0
.;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
0.95
P;D;.;D
Vest4
0.44
MVP
0.67
ClinPred
0.42
T
GERP RS
0.73
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

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: rs200088833; hg19: chr1-11807576; API