rs148798482

Variant summary

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

The NM_012344.4(NTSR2):​c.757C>T​(p.Arg253Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,612,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

NTSR2
NM_012344.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67
Variant links:
Genes affected
NTSR2 (HGNC:8040): (neurotensin receptor 2) The protein encoded by this gene belongs to the G protein-coupled receptor family that activate a phosphatidylinositol-calcium second messenger system. Binding and pharmacological studies demonstrate that this receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. However, unlike NT1 receptor, this gene recognizes, with high affinity, levocabastine, a histamine H1 receptor antagonist previously shown to compete with neurotensin for low-affinity binding sites in brain. These activities suggest that this receptor may be of physiological importance and that a natural agonist for the receptor may exist. [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=0.19895592).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTSR2NM_012344.4 linkc.757C>T p.Arg253Cys missense_variant Exon 2 of 4 ENST00000306928.6 NP_036476.2 O95665

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTSR2ENST00000306928.6 linkc.757C>T p.Arg253Cys missense_variant Exon 2 of 4 1 NM_012344.4 ENSP00000303686.5 O95665

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249434
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135032
show subpopulations
Gnomad AFR exome
AF:
0.0000622
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000431
AC:
63
AN:
1460742
Hom.:
0
Cov.:
31
AF XY:
0.0000454
AC XY:
33
AN XY:
726654
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000504
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000724
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.094
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.015
D
Polyphen
0.028
B
Vest4
0.23
MutPred
0.67
Loss of disorder (P = 0.0477);
MVP
0.77
MPC
0.20
ClinPred
0.50
D
GERP RS
2.5
Varity_R
0.20
gMVP
0.30

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: rs148798482; hg19: chr2-11802234; API