chr5-152404656-C-A

Variant summary

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

The NM_020167.5(NMUR2):​c.458G>T​(p.Arg153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

NMUR2
NM_020167.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59
Variant links:
Genes affected
NMUR2 (HGNC:16454): (neuromedin U receptor 2) This gene encodes a protein from the G-protein coupled receptor 1 family. This protein is a receptor for neuromedin U, which is a neuropeptide that is widely distributed in the gut and central nervous system. This receptor plays an important role in the regulation of food intake and body weight. [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
NMUR2NM_020167.5 linkc.458G>T p.Arg153Leu missense_variant Exon 1 of 4 ENST00000255262.4 NP_064552.3 Q9GZQ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NMUR2ENST00000255262.4 linkc.458G>T p.Arg153Leu missense_variant Exon 1 of 4 1 NM_020167.5 ENSP00000255262.4 Q9GZQ4
NMUR2ENST00000518933.1 linkn.273-6512G>T intron_variant Intron 2 of 3 3
ENSG00000286749ENST00000663460.1 linkn.216+29443C>A intron_variant Intron 1 of 3
ENSG00000286749ENST00000663819.1 linkn.183+29443C>A intron_variant Intron 1 of 3

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
151906
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
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:
0.000127
AC:
32
AN:
251162
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000839
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:
0.00
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461692
Hom.:
0
Cov.:
34
AF XY:
0.0000138
AC XY:
10
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000716
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152016
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000589
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
Bravo
AF:
0.0000340
ExAC
AF:
0.0000742
AC:
9

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.458G>T (p.R153L) alteration is located in exon 1 (coding exon 1) of the NMUR2 gene. This alteration results from a G to T substitution at nucleotide position 458, causing the arginine (R) at amino acid position 153 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
0.16
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.098
T
Eigen
Uncertain
0.31
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.59
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.72
D
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-3.8
D
REVEL
Benign
0.24
Sift
Benign
0.34
T
Sift4G
Benign
0.22
T
Polyphen
0.98
D
Vest4
0.66
MutPred
0.79
Loss of methylation at R153 (P = 0.0152);
MVP
0.42
MPC
0.66
ClinPred
0.43
T
GERP RS
5.3
Varity_R
0.37
gMVP
0.70

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: rs756384094; hg19: chr5-151784217; API