5-152395503-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020167.5(NMUR2):c.893G>C(p.Ser298Thr) variant causes a missense change. The variant allele was found at a frequency of 0.18 in 1,612,954 control chromosomes in the GnomAD database, including 28,613 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (2080 hom., cov: 30)
  • Exomes 𝑓: 0.18 (26533 hom.)
• Consequence: NMUR2 NM_020167.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00396955).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMUR2	NM_020167.5	c.893G>C	p.Ser298Thr	missense_variant	3/4	ENST00000255262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMUR2	ENST00000255262.4	c.893G>C	p.Ser298Thr	missense_variant	3/4	1	NM_020167.5	P1
	ENST00000663819.1	n.183+20290C>G		intron_variant, non_coding_transcript_variant
NMUR2	ENST00000518933.1	n.439G>C		non_coding_transcript_exon_variant	4/4	3
	ENST00000663460.1	n.216+20290C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21974 AN: 151722 Hom.: 2083 Cov.: 30

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.183 AC: 45986 AN: 250910 Hom.: 5346 AF XY: 0.182 AC XY: 24647 AN XY: 135596

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.0317

Gnomad SAS exome AF: 0.190

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.183 AC: 267914 AN: 1461114 Hom.: 26533 Cov.: 33 AF XY: 0.183 AC XY: 133010 AN XY: 726870

Gnomad4 AFR exome AF: 0.0382

Gnomad4 AMR exome AF: 0.339

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: 21963 AN: 151840 Hom.: 2080 Cov.: 30 AF XY: 0.145 AC XY: 10776 AN XY: 74158

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.153

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: 0.162 Hom.: 1638

Bravo AF: 0.147

TwinsUK AF: 0.205 AC: 759

ALSPAC AF: 0.193 AC: 744

ESP6500AA AF: 0.0531 AC: 234

ESP6500EA AF: 0.181 AC: 1556

ExAC AF: 0.174 AC: 21179

Asia WGS AF: 0.0850 AC: 297 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	16
Dann	Benign	0.22
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.056	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.13
ClinPred		0.0074	T
GERP RS		3.0
Varity_R		0.044
gMVP		0.37

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

Other links and lift over

dbSNP: rs4958535; hg19: chr5-151775064; COSMIC: COSV54916853;