rs796052202

Positions:

• chr1-162357021-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000361897.10(NOS1AP):​c.824C>T​(p.Ser275Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 0.0000014 (0 hom.)
• Consequence: NOS1AP ENST00000361897.10 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.43

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16762254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.824C>T	p.Ser275Phe	missense_variant	8/10	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.809C>T	p.Ser270Phe	missense_variant	8/10		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.824C>T	p.Ser275Phe	missense_variant	8/10	1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.809C>T	p.Ser270Phe	missense_variant	8/10	1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.809C>T	p.Ser270Phe	missense_variant, NMD_transcript_variant	8/11	1		ENSP00000396713

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461708 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.092
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Uncertain	0.55	.;D
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.9	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.17
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.017	D;D
Polyphen		0.41	.;B
Vest4		0.27
MutPred		0.20		.;Loss of phosphorylation at S275 (P = 0.0075);
MVP		0.73
MPC		0.089
ClinPred		0.27	T
GERP RS		4.6
Varity_R		0.087
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs796052202; hg19: chr1-162326811; COSMIC: COSV100723096; COSMIC: COSV100723096;