Variant rs348624 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014697.3(NOS1AP):c.1002C>T(p.Arg334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,774 control chromosomes in the GnomAD database, including 20,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4519 hom., cov: 33)

Exomes 𝑓: 0.13 ( 16125 hom. )

Consequence

NOS1AP
NM_014697.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.73

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 1-162365466-C-T is Benign according to our data. Variant chr1-162365466-C-T is described in ClinVar as [Benign]. Clinvar id is 1233083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NOS1AP	NM_014697.3 linkuse as main transcript	c.1002C>T	p.Arg334=	synonymous_variant	9/10	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2 linkuse as main transcript	c.987C>T	p.Arg329=	synonymous_variant	9/10		NP_001158229.1
NOS1AP	NM_001126060.2 linkuse as main transcript	c.117C>T	p.Arg39=	synonymous_variant	1/2		NP_001119532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10 linkuse as main transcript	c.1002C>T	p.Arg334=	synonymous_variant	9/10	1	NM_014697.3	ENSP00000355133		O75052-1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31271

AN:

152030

Hom.:

4502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.169

AC:

42412

AN:

250858

Hom.:

4610

AF XY:

0.167

AC XY:

22721

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.134

AC:

196212

AN:

1461626

Hom.:

16125

Cov.:

AF XY:

0.138

AC XY:

100044

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.206

AC:

31322

AN:

152148

Hom.:

4519

Cov.:

AF XY:

0.207

AC XY:

15399

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.142

Hom.:

2506

Bravo

AF:

0.219

Asia WGS

AF:

0.233

AC:

810

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.127

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nephrotic syndrome, type 22

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

0.86

DANN

Benign

0.82

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