rs3751284

chr1-162343945-C-Achr1-162343945-C-Gchr1-162343945-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_014697.3(NOS1AP):c.564C>A(p.Ser188Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S188S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NOS1AP NM_014697.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity CAPON_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18367597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.564C>A	p.Ser188Arg	missense_variant	6/10	ENST00000361897.10
NOS1AP	NM_001164757.2	c.549C>A	p.Ser183Arg	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.564C>A	p.Ser188Arg	missense_variant	6/10	1	NM_014697.3
NOS1AP	ENST00000530878.5	c.549C>A	p.Ser183Arg	missense_variant	6/10	1		P1
NOS1AP	ENST00000430120.3	c.549C>A	p.Ser183Arg	missense_variant, NMD_transcript_variant	6/11	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	3.3
Dann	Benign	0.97
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Uncertain	-0.26	T
MutationTaster	Benign	0.90	N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.44
Sift	Benign	0.14	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.91	.;P
Vest4		0.41
MutPred		0.20		.;Loss of phosphorylation at S188 (P = 0.0087);
MVP		0.60
MPC		0.18
ClinPred		0.97	D
GERP RS		-8.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-162313735;