chr20-64106039-C-T

Variant summary

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

The NM_005286.4(NPBWR2):​c.793G>A​(p.Val265Met) variant causes a missense change. The variant allele was found at a frequency of 0.000041 in 1,610,830 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

NPBWR2
NM_005286.4 missense

Scores

1
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3067881).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPBWR2NM_005286.4 linkc.793G>A p.Val265Met 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.793G>A p.Val265Met missense_variant Exon 2 of 2 NM_005286.4 ENSP00000508236.1 P48146
NPBWR2ENST00000369768.1 linkc.793G>A p.Val265Met missense_variant Exon 1 of 1 6 ENSP00000358783.1 P48146
MYT1ENST00000659024.1 linkc.-313+3484C>T intron_variant Intron 1 of 16 ENSP00000499493.1 Q6P6D5
MYT1ENST00000644172.2 linkc.22+3484C>T intron_variant Intron 1 of 2 ENSP00000493561.2 A0A2R8Y3S5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152078
Hom.:
0
Cov.:
32
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:
0.000829
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000972
AC:
24
AN:
246970
Hom.:
0
AF XY:
0.000142
AC XY:
19
AN XY:
134236
show subpopulations
Gnomad AFR exome
AF:
0.000125
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000622
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000425
AC:
62
AN:
1458634
Hom.:
0
Cov.:
36
AF XY:
0.0000634
AC XY:
46
AN XY:
725486
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000499
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000990
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74402
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:
0.000830
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000828
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.793G>A (p.V265M) 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 793, causing the valine (V) at amino acid position 265 to be replaced by a methionine (M). 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
0.60
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.31
T
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-2.5
N
REVEL
Uncertain
0.36
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.054
T
Polyphen
1.0
D
Vest4
0.35
MutPred
0.60
Gain of helix (P = 0.0425);
MVP
0.79
MPC
0.89
ClinPred
0.42
T
GERP RS
4.0
Varity_R
0.52
gMVP
0.58

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.

Other links and lift over

dbSNP: rs778749703; hg19: chr20-62737392; COSMIC: COSV100871164; API