chr17-81902378-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_148896.5(NPB):c.101C>T(p.Ser34Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 1,343,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NPB
NM_148896.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.123

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spastic paraplegia 82, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

PCYT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061574996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148896.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPB	NM_148896.5	MANE Select	c.101C>T	p.Ser34Phe	missense	Exon 1 of 2	NP_683694.1	Q8NG41
PCYT2	NM_002861.5	MANE Select	c.*2455G>A		3_prime_UTR	Exon 13 of 13	NP_002852.1	Q99447-1
PCYT2	NM_001184917.3		c.*2455G>A		3_prime_UTR	Exon 14 of 14	NP_001171846.1	Q99447-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPB	ENST00000333383.8	TSL:1 MANE Select	c.101C>T	p.Ser34Phe	missense	Exon 1 of 2	ENSP00000332766.7	Q8NG41
PCYT2	ENST00000538936.7	TSL:1 MANE Select	c.*2455G>A		3_prime_UTR	Exon 13 of 13	ENSP00000439245.3	Q99447-1
NPB	ENST00000573081.1	TSL:6	c.101C>T	p.Ser34Phe	missense	Exon 1 of 1	ENSP00000461824.1	I3NI19

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

778

AF XY:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000336

AC:

AN:

1190936

Hom.:

Cov.:

AF XY:

0.00000349

AC XY:

AN XY:

573210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23370

American (AMR)

AF:

0.000113

AC:

AN:

8870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16500

East Asian (EAS)

AF:

0.00

AC:

AN:

26940

South Asian (SAS)

AF:

0.00

AC:

AN:

47514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3326

European-Non Finnish (NFE)

AF:

0.00000304

AC:

AN:

986394

Other (OTH)

AF:

0.00

AC:

AN:

49190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.000131

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.014

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.78

M_CAP

Benign

0.083

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

PhyloP100

-0.12

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

2.4

REVEL

Benign

0.033

Sift

Benign

0.23

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.15

MutPred

0.29

Loss of disorder (P = 0.0076)

MVP

0.014

MPC

0.31

ClinPred

0.068

GERP RS

-0.52

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.064

gMVP

0.16

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over