Variant 15-84655364-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_205858.2(NMB):c.371T>A(p.Met124Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

NMB
NM_205858.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0620

Variant links:

Genes affected

NMB (HGNC:7842): (neuromedin B) This gene encodes a member of the bombesin-like family of neuropeptides, which negatively regulate eating behavior. The encoded protein may regulate colonic smooth muscle contraction through binding to its cognate receptor, the neuromedin B receptor (NMBR). Polymorphisms of this gene may be associated with hunger, weight gain and obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

NMB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.105456024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMB	NM_021077.4 linkuse as main transcript	c.*10T>A		3_prime_UTR_variant	3/3	ENST00000360476.8	NP_066563.2	P08949-1
NMB	NM_205858.2 linkuse as main transcript	c.371T>A	p.Met124Lys	missense_variant	3/3		NP_995580.1	P08949-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMB	ENST00000394588.3 linkuse as main transcript	c.371T>A	p.Met124Lys	missense_variant	3/3	1		ENSP00000378089.3		P08949-2
NMB	ENST00000360476 linkuse as main transcript	c.*10T>A		3_prime_UTR_variant	3/3	1	NM_021077.4	ENSP00000353664.3		P08949-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 13, 2024

The c.371T>A (p.M124K) alteration is located in exon 3 (coding exon 3) of the NMB gene. This alteration results from a T to A substitution at nucleotide position 371, causing the methionine (M) at amino acid position 124 to be replaced by a lysine (K). 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

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.0

DANN

Benign

0.71

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.27

M_CAP

Benign

0.0075

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.6

REVEL

Benign

0.024

Sift

Uncertain

0.027

Sift4G

Uncertain

0.0070

Polyphen

0.36

Vest4

0.32

MutPred

0.38

Gain of ubiquitination at M124 (P = 0.0029);

MVP

0.13

MPC

0.26

ClinPred

0.16

GERP RS

1.3

gMVP

0.19

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over