Variant 1-162343945-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014697.3(NOS1AP):c.564C>T(p.Ser188Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,488 control chromosomes in the GnomAD database, including 115,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10687 hom., cov: 31)

Exomes 𝑓: 0.37 ( 104780 hom. )

Consequence

NOS1AP
NM_014697.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.25

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-162343945-C-T is Benign according to our data. Variant chr1-162343945-C-T is described in ClinVar as [Benign]. Clinvar id is 1293319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3 linkuse as main transcript	c.564C>T	p.Ser188Ser	synonymous_variant	6/10	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001164757.2 linkuse as main transcript	c.549C>T	p.Ser183Ser	synonymous_variant	6/10		NP_001158229.1	O75052-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOS1AP	ENST00000361897.10 linkuse as main transcript	c.564C>T	p.Ser188Ser	synonymous_variant	6/10	1	NM_014697.3	ENSP00000355133.5	O75052-1
NOS1AP	ENST00000530878.5 linkuse as main transcript	c.549C>T	p.Ser183Ser	synonymous_variant	6/10	1		ENSP00000431586.1	O75052-3
NOS1AP	ENST00000430120.3 linkuse as main transcript	n.549C>T		non_coding_transcript_exon_variant	6/11	1		ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55643

AN:

151820

Hom.:

10669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.372

GnomAD3 exomes

AF:

0.412

AC:

103489

AN:

250894

Hom.:

22393

AF XY:

0.414

AC XY:

56126

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.598

Gnomad SAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.373

AC:

545356

AN:

1461546

Hom.:

104780

Cov.:

AF XY:

0.376

AC XY:

273421

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.385

Gnomad4 EAS exome

AF:

0.597

Gnomad4 SAS exome

AF:

0.460

Gnomad4 FIN exome

AF:

0.460

Gnomad4 NFE exome

AF:

0.352

Gnomad4 OTH exome

AF:

0.379

GnomAD4 genome

AF:

0.367

AC:

55692

AN:

151942

Hom.:

10687

Cov.:

AF XY:

0.378

AC XY:

28049

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.289

Gnomad4 AMR

AF:

0.432

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.601

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.327

Hom.:

4123

Bravo

AF:

0.358

Asia WGS

AF:

0.486

AC:

1687

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.353

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	GeneDx	Sep 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.7

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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