7-34844932-T-G

Variant names:

• chr7-34844932-T-G
• rs143774126
• NM_207172.2:c.794T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_207172.2(NPSR1):​c.794T>G​(p.Ile265Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPSR1 NM_207172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

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-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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.794T>G	p.Ile265Ser	missense_variant	Exon 7 of 9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.794T>G	p.Ile265Ser	missense_variant	Exon 7 of 9	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251468 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135904

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.;.;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.4	M;.;M;.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Benign	0.18	T;D;T;T;T
Polyphen		0.97	D;P;D;P;P
Vest4		0.69
MutPred		0.69		Gain of disorder (P = 4e-04);.;Gain of disorder (P = 4e-04);.;Gain of disorder (P = 4e-04);
MVP		0.92
MPC		0.11
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.80
gMVP		0.73

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

LitVar

Other links and lift over

dbSNP: rs143774126; hg19: chr7-34884544;