rs348624

chr1-162365466-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.73

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 -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	UniProt
NOS1AP	NM_014697.3	c.1002C>T	p.Arg334=	synonymous_variant	9/10	ENST00000361897.10
NOS1AP	NM_001164757.2	c.987C>T	p.Arg329=	synonymous_variant	9/10
NOS1AP	NM_001126060.2	c.117C>T	p.Arg39=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.1002C>T	p.Arg334=	synonymous_variant	9/10	1	NM_014697.3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31271 AN: 152030 Hom.: 4502 Cov.: 33

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

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.: 39 AF XY: 0.138 AC XY: 100044 AN XY: 727150

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.: 33 AF XY: 0.207 AC XY: 15399 AN XY: 74394

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 28, 2019

- -

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

Other links and lift over

dbSNP: rs348624; hg19: chr1-162335256; COSMIC: COSV62633145; COSMIC: COSV62633145;