rs796052201

chr1-162367222-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014697.3(NOS1AP):c.1276G>A(p.Val426Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NOS1AP NM_014697.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.60

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31002825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.1276G>A	p.Val426Met	missense_variant	10/10	ENST00000361897.10
NOS1AP	NM_001164757.2	c.1261G>A	p.Val421Met	missense_variant	10/10
NOS1AP	NM_001126060.2	c.391G>A	p.Val131Met	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.1276G>A	p.Val426Met	missense_variant	10/10	1	NM_014697.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Uncertain:1

Uncertain significance, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.40	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.70	N;N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.052	T;T;D
Polyphen		0.84	.;P;.
Vest4		0.52
MutPred		0.30		.;Loss of sheet (P = 0.0063);.;
MVP		0.70
MPC		1.8
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.14
gMVP		0.21

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: rs796052201; hg19: chr1-162337012;