rs764132367

Variant summary

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

The NM_005286.4(NPBWR2):​c.887G>T​(p.Ser296Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S296N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NPBWR2
NM_005286.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.48
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]
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]

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=0.09870511).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPBWR2NM_005286.4 linkc.887G>T p.Ser296Ile missense_variant Exon 2 of 2 ENST00000684052.1 NP_005277.2 P48146

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPBWR2ENST00000684052.1 linkc.887G>T p.Ser296Ile missense_variant Exon 2 of 2 NM_005286.4 ENSP00000508236.1 P48146
NPBWR2ENST00000369768.1 linkc.887G>T p.Ser296Ile missense_variant Exon 1 of 1 6 ENSP00000358783.1 P48146
MYT1ENST00000659024.1 linkc.-313+3390C>A intron_variant Intron 1 of 16 ENSP00000499493.1 Q6P6D5
MYT1ENST00000644172.2 linkc.22+3390C>A intron_variant Intron 1 of 2 ENSP00000493561.2 A0A2R8Y3S5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000800
AC:
2
AN:
250106
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135630
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460688
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
726648
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
9.7
DANN
Benign
0.62
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.28
N
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.099
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.94
L
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.095
Sift
Benign
0.056
T
Sift4G
Benign
0.066
T
Polyphen
0.0070
B
Vest4
0.040
MutPred
0.52
Gain of sheet (P = 0.0477);
MVP
0.40
MPC
0.29
ClinPred
0.64
D
GERP RS
1.3
Varity_R
0.23
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs764132367; hg19: chr20-62737298; API