Variant rs325465 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_207172.2(NPSR1):c.427A>C(p.Ser143Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. S143G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NPSR1
NM_207172.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

NPSR1 (HGNC:23631): (neuropeptide S receptor 1) This gene encodes a member of the vasopressin/oxytocin subfamily of G protein-coupled receptors. The encoded membrane protein acts as a receptor for neuropeptide S and affects a variety of cellular processes through its signaling. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Polymorphisms in this gene have also been associated with asthma susceptibility, panic disorders, inflammatory bowel disease, and rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPSR1 links:

NPSR1-AS1 (HGNC:22128): (NPSR1 antisense RNA 1) This gene is located within a region that has been associated with asthma susceptibility. The locus is considered non-protein-coding based on lack of protein homology and a lack of experimental support for an encoded protein. Three alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2010]

NPSR1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2 link	c.427A>C	p.Ser143Arg	missense_variant	Exon 4 of 9	ENST00000360581.6	NP_997055.1	Q6W5P4-1A0A090N8Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6 link	c.427A>C	p.Ser143Arg	missense_variant	Exon 4 of 9	1	NM_207172.2	ENSP00000353788.1		Q6W5P4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250864

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135620

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461360

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

D;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.96

D;D;D;D

MetaSVM

Uncertain

0.60

MutationAssessor

Pathogenic

3.0

M;M;.;M

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.2

D;D;D;D

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.79

MutPred

0.84

Gain of catalytic residue at S143 (P = 0.1025);Gain of catalytic residue at S143 (P = 0.1025);.;Gain of catalytic residue at S143 (P = 0.1025);

MVP

0.97

MPC

0.041

ClinPred

0.99

GERP RS

4.2

Varity_R

0.98

gMVP

0.97

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over