Variant chr10-127552625-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001030013.2(NPS):c.256A>G(p.Arg86Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00128 in 1,612,138 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 13 hom. )

Consequence

NPS
NM_001030013.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

NPS (HGNC:33940): (neuropeptide S) Predicted to be involved in positive regulation of GABAergic synaptic transmission; positive regulation of action potential; and positive regulation of glutamatergic synaptic transmission. Predicted to act upstream of or within visual learning. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

NPS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074257255).

BP6

Variant 10-127552625-A-G is Benign according to our data. Variant chr10-127552625-A-G is described in ClinVar as [Benign]. Clinvar id is 787371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00653 (995/152304) while in subpopulation AFR AF= 0.0225 (937/41566). AF 95% confidence interval is 0.0213. There are 11 homozygotes in gnomad4. There are 484 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPS	NM_001030013.2 linkuse as main transcript	c.256A>G	p.Arg86Gly	missense_variant	3/3	ENST00000398023.3	NP_001025184.1	P0C0P6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPS	ENST00000398023.3 linkuse as main transcript	c.256A>G	p.Arg86Gly	missense_variant	3/3	5	NM_001030013.2	ENSP00000381105.2		P0C0P6

Frequencies

GnomAD3 genomes

AF:

0.00651

AC:

990

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

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:

0.0000882

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00168

AC:

418

AN:

249034

Hom.:

AF XY:

0.00127

AC XY:

172

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000731

AC:

1067

AN:

1459834

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

460

AN XY:

726352

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00653

AC:

995

AN:

152304

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

484

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0225

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00787

ESP6500AA

AF:

0.0198

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00198

AC:

239

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.37

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.90

MVP

0.64

MPC

0.019

ClinPred

0.049

GERP RS

5.6

Varity_R

0.80

gMVP

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over