20-64106233-C-T

Variant names:

Variant summary

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

The NM_005286.4(NPBWR2):c.599G>A(p.Ser200Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,612,636 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

NPBWR2
NM_005286.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.687

Variant links:

Genes affected

NPBWR2 (HGNC:4530): (neuropeptides B and W receptor 2) The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor. The encoded protein is similar in sequence to another G protein-coupled receptor (GPR7), and it is structurally similar to opioid and somatostatin receptors. This protein binds neuropeptides B and W. This gene is intronless and is expressed primarily in the frontal cortex of the brain. [provided by RefSeq, Jul 2008]

NPBWR2 links:

MYT1 (HGNC:7622): (myelin transcription factor 1) The protein encoded by this gene is a member of a family of neural specific, zinc finger-containing DNA-binding proteins. The protein binds to the promoter regions of proteolipid proteins of the central nervous system and plays a role in the developing nervous system. [provided by RefSeq, Jul 2008]

MYT1 links:

Genome browser will be placed here

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=0.0860481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPBWR2	NM_005286.4 link	c.599G>A	p.Ser200Asn	missense_variant	Exon 2 of 2	ENST00000684052.1	NP_005277.2	P48146

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPBWR2	ENST00000684052.1 link	c.599G>A	p.Ser200Asn	missense_variant	Exon 2 of 2		NM_005286.4	ENSP00000508236.1	P48146
NPBWR2	ENST00000369768.1 link	c.599G>A	p.Ser200Asn	missense_variant	Exon 1 of 1	6		ENSP00000358783.1	P48146
MYT1	ENST00000659024.1 link	c.-313+3678C>T		intron_variant	Intron 1 of 16			ENSP00000499493.1	Q6P6D5
MYT1	ENST00000644172.2 link	c.22+3678C>T		intron_variant	Intron 1 of 2			ENSP00000493561.2	A0A2R8Y3S5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

249016

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000170

AC:

249

AN:

1460438

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000215

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000981

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.599G>A (p.S200N) alteration is located in exon 1 (coding exon 1) of the NPBWR2 gene. This alteration results from a G to A substitution at nucleotide position 599, causing the serine (S) at amino acid position 200 to be replaced by an asparagine (N). 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

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.032

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.53

M_CAP

Benign

0.010

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.53

REVEL

Benign

0.080

Sift

Benign

0.39

Sift4G

Benign

0.54

Polyphen

0.044

Vest4

0.045

MVP

0.51

MPC

0.82

ClinPred

0.13

GERP RS

2.9

Varity_R

0.17

gMVP

0.55

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