Variant chr1-162333056-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_014697.3(NOS1AP):c.384C>T(p.Ile128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,613,890 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 13 hom. )

Consequence

NOS1AP
NM_014697.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.16

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 1-162333056-C-T is Benign according to our data. Variant chr1-162333056-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 496432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-162333056-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.16 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3 linkuse as main transcript	c.384C>T	p.Ile128=	synonymous_variant	5/10	ENST00000361897.10
NOS1AP	NM_001164757.2 linkuse as main transcript	c.369C>T	p.Ile123=	synonymous_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10 linkuse as main transcript	c.384C>T	p.Ile128=	synonymous_variant	5/10	1	NM_014697.3		O75052-1
NOS1AP	ENST00000530878.5 linkuse as main transcript	c.369C>T	p.Ile123=	synonymous_variant	5/10	1		P1	O75052-3
NOS1AP	ENST00000430120.3 linkuse as main transcript	c.369C>T	p.Ile123=	synonymous_variant, NMD_transcript_variant	5/11	1

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

533

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00414

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00354

AC:

889

AN:

251252

Hom.:

AF XY:

0.00358

AC XY:

486

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00360

AC:

5263

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

2649

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.0150

Gnomad4 NFE exome

AF:

0.00366

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00350

AC:

533

AN:

152290

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.00415

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00302

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jan 26, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	NOS1AP: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.80

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