17-81902740-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_148896.5(NPB):c.370G>A(p.Ala124Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000611 in 1,605,828 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 1 hom. )

Consequence

NPB
NM_148896.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.74

Variant links:

Genes affected

NPB (HGNC:30099): (neuropeptide B) This gene encodes a member of the neuropeptide B/W family of proteins and preproprotein that is proteolytically processed to generate multiple protein products. The encoded products include neuropeptide B-23 and a C-terminally extended form, neuropeptide B-29, which are characterized by an N-terminal brominated tryptophan amino acid. Both of the encoded peptides bind with higher affinity to neuropeptide B/W (NPB/W) receptor 1 compared to the related NPB/W receptor 2. These peptides may regulate feeding, pain perception, and stress in rodents. [provided by RefSeq, Jul 2015]

NPB links:

PCYT2 (HGNC:8756): (phosphate cytidylyltransferase 2, ethanolamine) This gene encodes an enzyme that catalyzes the formation of CDP-ethanolamine from CTP and phosphoethanolamine in the Kennedy pathway of phospholipid synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

PCYT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010819614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPB	NM_148896.5 link	c.370G>A	p.Ala124Thr	missense_variant	Exon 2 of 2	ENST00000333383.8	NP_683694.1	Q8NG41
PCYT2	NM_002861.5 link	c.*2093C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000538936.7	NP_002852.1	Q99447-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPB	ENST00000333383.8 link	c.370G>A	p.Ala124Thr	missense_variant	Exon 2 of 2	1	NM_148896.5	ENSP00000332766.7	Q8NG41
PCYT2	ENST00000538936 link	c.*2093C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_002861.5	ENSP00000439245.3	Q99447-1
NPB	ENST00000573081.1 link	c.463G>A	p.Ala155Thr	missense_variant	Exon 1 of 1	6		ENSP00000461824.1	I3NI19

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000637

AC:

147

AN:

230892

Hom.:

AF XY:

0.000692

AC XY:

AN XY:

127238

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.000613

Gnomad NFE exome

AF:

0.000828

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.000629

AC:

914

AN:

1453544

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

500

AN XY:

723034

show subpopulations

Gnomad4 AFR exome

AF:

0.0000911

Gnomad4 AMR exome

AF:

0.000338

Gnomad4 ASJ exome

AF:

0.0000771

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.000839

Gnomad4 NFE exome

AF:

0.000609

Gnomad4 OTH exome

AF:

0.000699

GnomAD4 genome

AF:

0.000440

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000505

Hom.:

Bravo

AF:

0.000366

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000817

AC:

ExAC

AF:

0.000659

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370G>A (p.A124T) alteration is located in exon 2 (coding exon 2) of the NPB gene. This alteration results from a G to A substitution at nucleotide position 370, causing the alanine (A) at amino acid position 124 to be replaced by a threonine (T). 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

0.093

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.020

DANN

Benign

0.86

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.54

.;N

REVEL

Benign

0.030

Sift

Benign

0.29

.;T

Sift4G

Benign

0.50

T;T

Polyphen

0.61

.;P

Vest4

0.075

MVP

0.014

MPC

0.27

ClinPred

0.016

GERP RS

-3.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.9

Varity_R

0.030

gMVP

0.13

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over