1-162343945-C-T

Variant names:

• chr1-162343945-C-T
• rs3751284
• NM_014697.3:c.564C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014697.3(NOS1AP):​c.564C>T​(p.Ser188Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,488 control chromosomes in the GnomAD database, including 115,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10687 hom., cov: 31)
  • Exomes 𝑓: 0.37 (104780 hom.)
• Consequence: NOS1AP NM_014697.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.25
• Publications: 25 publications found

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]

NOS1AP Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 22

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-162343945-C-T is Benign according to our data. Variant chr1-162343945-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.564C>T	p.Ser188Ser	synonymous_variant	Exon 6 of 10	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.549C>T	p.Ser183Ser	synonymous_variant	Exon 6 of 10		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.564C>T	p.Ser188Ser	synonymous_variant	Exon 6 of 10	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.549C>T	p.Ser183Ser	synonymous_variant	Exon 6 of 10	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.549C>T		non_coding_transcript_exon_variant	Exon 6 of 11	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55643 AN: 151820 Hom.: 10669 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.372

GnomAD2 exomes AF: 0.412 AC: 103489 AN: 250894 AF XY: 0.414

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.598

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.373 AC: 545356 AN: 1461546 Hom.: 104780 Cov.: 50 AF XY: 0.376 AC XY: 273421 AN XY: 727102

African (AFR) AF: 0.284 AC: 9521 AN: 33474

American (AMR) AF: 0.479 AC: 21411 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 10048 AN: 26126

East Asian (EAS) AF: 0.597 AC: 23697 AN: 39696

South Asian (SAS) AF: 0.460 AC: 39668 AN: 86244

European-Finnish (FIN) AF: 0.460 AC: 24569 AN: 53408

Middle Eastern (MID) AF: 0.377 AC: 2171 AN: 5766

European-Non Finnish (NFE) AF: 0.352 AC: 391362 AN: 1111740

Other (OTH) AF: 0.379 AC: 22909 AN: 60384

GnomAD4 genome AF: 0.367 AC: 55692 AN: 151942 Hom.: 10687 Cov.: 31 AF XY: 0.378 AC XY: 28049 AN XY: 74262

African (AFR) AF: 0.289 AC: 11977 AN: 41438

American (AMR) AF: 0.432 AC: 6589 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3095 AN: 5150

South Asian (SAS) AF: 0.468 AC: 2248 AN: 4806

European-Finnish (FIN) AF: 0.473 AC: 4984 AN: 10530

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24226 AN: 67968

Other (OTH) AF: 0.371 AC: 782 AN: 2108

Alfa AF: 0.327 Hom.: 4157

Bravo AF: 0.358

Asia WGS AF: 0.486 AC: 1687 AN: 3478

EpiCase AF: 0.352

EpiControl AF: 0.353

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.7
DANN	Benign	0.80
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3751284; hg19: chr1-162313735; COSMIC: COSV62632915; COSMIC: COSV62632915;