chr17-81902717-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_148896.5(NPB):c.347C>T(p.Ser116Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000995 in 1,608,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NPB
NM_148896.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35024554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPB	NM_148896.5 link	c.347C>T	p.Ser116Phe	missense_variant	Exon 2 of 2	ENST00000333383.8	NP_683694.1	Q8NG41
PCYT2	NM_002861.5 link	c.*2116G>A		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.347C>T	p.Ser116Phe	missense_variant	Exon 2 of 2	1	NM_148896.5	ENSP00000332766.7	Q8NG41
PCYT2	ENST00000538936 link	c.*2116G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_002861.5	ENSP00000439245.3	Q99447-1
NPB	ENST00000573081.1 link	c.440C>T	p.Ser147Phe	missense_variant	Exon 1 of 1	6		ENSP00000461824.1	I3NI19

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

234922

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129016

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000567

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000971

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1456294

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724450

show subpopulations

Gnomad4 AFR exome

AF:

0.0000906

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.347C>T (p.S116F) alteration is located in exon 2 (coding exon 2) of the NPB gene. This alteration results from a C to T substitution at nucleotide position 347, causing the serine (S) at amino acid position 116 to be replaced by a phenylalanine (F). 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

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;D

Eigen

Benign

0.17

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.78

T;T

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

2.0

.;M

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.6

.;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.99

.;D

Vest4

0.58

MutPred

0.42

.;Loss of catalytic residue at S116 (P = 0.0645);

MVP

0.030

MPC

0.95

ClinPred

0.94

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.44

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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