Variant 1-162300673-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014697.3(NOS1AP):c.311G>A(p.Ser104Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,614,034 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 15 hom. )

Consequence

NOS1AP
NM_014697.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.86

Variant links:

Genes affected

NOS1AP (HGNC:16859): (nitric oxide synthase 1 adaptor protein) This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2009]

NOS1AP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009107232).

BP6

Variant 1-162300673-G-A is Benign according to our data. Variant chr1-162300673-G-A is described in ClinVar as [Benign]. Clinvar id is 714274.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3 linkuse as main transcript	c.311G>A	p.Ser104Asn	missense_variant	4/10	ENST00000361897.10
NOS1AP	NM_001164757.2 linkuse as main transcript	c.296G>A	p.Ser99Asn	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10 linkuse as main transcript	c.311G>A	p.Ser104Asn	missense_variant	4/10	1	NM_014697.3		O75052-1
NOS1AP	ENST00000530878.5 linkuse as main transcript	c.296G>A	p.Ser99Asn	missense_variant	4/10	1		P1	O75052-3
NOS1AP	ENST00000430120.3 linkuse as main transcript	c.296G>A	p.Ser99Asn	missense_variant, NMD_transcript_variant	4/11	1

Frequencies

GnomAD3 genomes

AF:

0.00331

AC:

503

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00340

AC:

854

AN:

251438

Hom.:

AF XY:

0.00346

AC XY:

470

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00355

AC:

5184

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

2599

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.00360

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.00330

AC:

503

AN:

152238

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.00379

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.00215

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00330

AC:

400

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00267

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.050

Eigen_PC

Benign

0.082

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.11

Sift

Benign

0.37

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.011

.;B

Vest4

0.084

MVP

0.31

MPC

1.1

ClinPred

0.0094

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.82

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

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