Genetic Variant NMUR2:p.Phe315Leu (chr5-152392494-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_020167.5(NMUR2):c.945C>A(p.Phe315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,609,094 control chromosomes in the GnomAD database, including 28,565 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.14 ( 2087 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26478 hom. )

Consequence

NMUR2
NM_020167.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

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:

ENSG00000286749 (HGNC:):

ENSG00000286749 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMUR2	NM_020167.5 link	c.945C>A	p.Phe315Leu	missense_variant	Exon 4 of 4	ENST00000255262.4	NP_064552.3	Q9GZQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NMUR2	ENST00000255262.4 link	c.945C>A	p.Phe315Leu	missense_variant	Exon 4 of 4	1	NM_020167.5	ENSP00000255262.4	Q9GZQ4
ENSG00000286749	ENST00000663460.1 link	n.216+17281G>T		intron_variant	Intron 1 of 3
ENSG00000286749	ENST00000663819.1 link	n.183+17281G>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22042

AN:

152046

Hom.:

2090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0345

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.184

AC:

45861

AN:

249682

Hom.:

5328

AF XY:

0.182

AC XY:

24570

AN XY:

134902

show subpopulations

Gnomad AFR exome

AF:

0.0417

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.0318

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.183

AC:

266695

AN:

1456930

Hom.:

26478

Cov.:

AF XY:

0.183

AC XY:

132381

AN XY:

724466

show subpopulations

Gnomad4 AFR exome

AF:

0.0382

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.0232

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.145

AC:

22031

AN:

152164

Hom.:

2087

Cov.:

AF XY:

0.145

AC XY:

10821

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.0346

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.169

Hom.:

5802

Bravo

AF:

0.147

TwinsUK

AF:

0.205

AC:

759

ALSPAC

AF:

0.193

AC:

744

ESP6500AA

AF:

0.0533

AC:

235

ESP6500EA

AF:

0.181

AC:

1556

ExAC

AF:

0.174

AC:

21166

Asia WGS

AF:

0.0850

AC:

297

AN:

3478

EpiCase

AF:

0.187

EpiControl

AF:

0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.22

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.15

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.088

Sift

Benign

0.44

Sift4G

Benign

0.36

Polyphen

0.010

Vest4

0.22

MutPred

0.44

Loss of glycosylation at S312 (P = 0.0853);

MPC

0.19

ClinPred

0.024

GERP RS

2.2

Varity_R

0.27

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.35

Position offset: 7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over