1-162333056-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.16

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]

ACMG classification

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 GnomAd at 2 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 533 AN: 152172 Hom.: 2 Cov.: 32

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.: 1 AF XY: 0.00358 AC XY: 486 AN XY: 135780

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.: 13 Cov.: 30 AF XY: 0.00364 AC XY: 2649 AN XY: 727096

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.: 2 Cov.: 32 AF XY: 0.00416 AC XY: 310 AN XY: 74470

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.: 2

Bravo AF: 0.00224

Asia WGS AF: 0.000289 AC: 1 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

Submissions by phenotype

not provided Benign:3

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs41271969; hg19: chr1-162302846;