Variant 5-152404887-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020167.5(NMUR2):c.227T>G(p.Met76Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,614,094 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00072 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

NMUR2
NM_020167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.99

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]

NMUR2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMUR2	NM_020167.5 linkuse as main transcript	c.227T>G	p.Met76Arg	missense_variant	1/4	ENST00000255262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NMUR2	ENST00000255262.4 linkuse as main transcript	c.227T>G	p.Met76Arg	missense_variant	1/4	1	NM_020167.5	P1
	ENST00000663819.1 linkuse as main transcript	n.183+29674A>C		intron_variant, non_coding_transcript_variant
NMUR2	ENST00000518933.1 linkuse as main transcript	n.273-6743T>G		intron_variant, non_coding_transcript_variant		3
	ENST00000663460.1 linkuse as main transcript	n.216+29674A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000717

AC:

109

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000589

AC:

148

AN:

251462

Hom.:

AF XY:

0.000640

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00100

AC:

1465

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000939

AC XY:

683

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00122

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152204

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000642

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.00142

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.227T>G (p.M76R) alteration is located in exon 1 (coding exon 1) of the NMUR2 gene. This alteration results from a T to G substitution at nucleotide position 227, causing the methionine (M) at amino acid position 76 to be replaced by an arginine (R). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Pathogenic

0.16

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.82

MVP

0.63

MPC

0.72

ClinPred

0.26

GERP RS

5.5

Varity_R

0.98

gMVP

0.88

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over