dbSNP rs201465953: NMUR2:p.Phe271Ser (chr5-152395584-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_020167.5(NMUR2):c.812T>C(p.Phe271Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000342 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F271L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NMUR2
NM_020167.5 missense, splice_region

Scores

Splicing: ADA: 0.5165

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMUR2	NM_020167.5 link	c.812T>C	p.Phe271Ser	missense_variant, splice_region_variant	Exon 3 of 4	ENST00000255262.4	NP_064552.3	Q9GZQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMUR2	ENST00000255262.4 link	c.812T>C	p.Phe271Ser	missense_variant, splice_region_variant	Exon 3 of 4	1	NM_020167.5	ENSP00000255262.4		Q9GZQ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250742

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111604

Other (OTH)

AF:

0.0000166

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000616

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.812T>C (p.F271S) alteration is located in exon 3 (coding exon 3) of the NMUR2 gene. This alteration results from a T to C substitution at nucleotide position 812, causing the phenylalanine (F) at amino acid position 271 to be replaced by a serine (S). 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

0.33

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PhyloP100

4.5

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.33

Sift

Benign

0.068

Sift4G

Benign

0.23

Polyphen

1.0

Vest4

0.73

MutPred

0.48

Loss of helix (P = 0.0376);

MVP

0.47

MPC

0.81

ClinPred

0.97

GERP RS

5.8

Varity_R

0.54

gMVP

0.51

Mutation Taster

=49/51

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.52

dbscSNV1_RF

Benign

0.52

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs201465953

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over