5-152404651-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_020167.5(NMUR2):c.463A>G(p.Lys155Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,614,066 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00066 (1 hom., cov: 31)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: NMUR2 NM_020167.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 4.73

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16248408).
• BP6: Variant 5-152404651-T-C is Benign according to our data. Variant chr5-152404651-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 764858.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMUR2	NM_020167.5	c.463A>G	p.Lys155Glu	missense_variant	1/4	ENST00000255262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMUR2	ENST00000255262.4	c.463A>G	p.Lys155Glu	missense_variant	1/4	1	NM_020167.5	P1
	ENST00000663819.1	n.183+29438T>C		intron_variant, non_coding_transcript_variant
NMUR2	ENST00000518933.1	n.273-6507A>G		intron_variant, non_coding_transcript_variant		3
	ENST00000663460.1	n.216+29438T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152096 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000478

GnomAD3 exomes AF: 0.000171 AC: 43 AN: 251196 Hom.: 0 AF XY: 0.000103 AC XY: 14 AN XY: 135824

Gnomad AFR exome AF: 0.00247

Gnomad AMR exome AF: 0.0000578

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: 0.000163

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1461852 Hom.: 0 Cov.: 34 AF XY: 0.0000426 AC XY: 31 AN XY: 727222

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.000134

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: 0.0000828

GnomAD4 genome AF: 0.000657 AC: 100 AN: 152214 Hom.: 1 Cov.: 31 AF XY: 0.000793 AC XY: 59 AN XY: 74426

Gnomad4 AFR AF: 0.00236

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: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.000752

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000222 AC: 27

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.463A>G (p.K155E) alteration is located in exon 1 (coding exon 1) of the NMUR2 gene. This alteration results from a A to G substitution at nucleotide position 463, causing the lysine (K) at amino acid position 155 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	0.0
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	-0.050	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.016	D
Sift4G	Benign	0.095	T
Polyphen		0.99	D
Vest4		0.71
MVP		0.88
MPC		0.68
ClinPred		0.065	T
GERP RS		5.3
Varity_R		0.64
gMVP		0.65

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: rs142503678; hg19: chr5-151784212;