NM_014697.3:c.384C>T

Variant names:

• chr1-162333056-C-T
• rs41271969
• NM_014697.3:c.384C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_014697.3(NOS1AP):​c.384C>T​(p.Ile128Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,613,890 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (13 hom.)
• Consequence: NOS1AP NM_014697.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.16
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 1-162333056-C-T is Benign according to our data. Variant chr1-162333056-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 496432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.384C>T	p.Ile128Ile	synonymous	Exon 5 of 10	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.369C>T	p.Ile123Ile	synonymous	Exon 5 of 10	NP_001158229.1	O75052-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.384C>T	p.Ile128Ile	synonymous	Exon 5 of 10	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.369C>T	p.Ile123Ile	synonymous	Exon 5 of 10	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.369C>T		non_coding_transcript_exon	Exon 5 of 11	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 533 AN: 152172 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00414

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00354 AC: 889 AN: 251252 AF XY: 0.00358

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0152

Gnomad NFE exome AF: 0.00393

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00360 AC: 5263 AN: 1461600 Hom.: 13 Cov.: 30 AF XY: 0.00364 AC XY: 2649 AN XY: 727096

African (AFR) AF: 0.000597 AC: 20 AN: 33476

American (AMR) AF: 0.000761 AC: 34 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00206 AC: 178 AN: 86250

European-Finnish (FIN) AF: 0.0150 AC: 803 AN: 53416

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5766

European-Non Finnish (NFE) AF: 0.00366 AC: 4069 AN: 1111770

Other (OTH) AF: 0.00242 AC: 146 AN: 60394

GnomAD4 genome AF: 0.00350 AC: 533 AN: 152290 Hom.: 2 Cov.: 32 AF XY: 0.00416 AC XY: 310 AN XY: 74470

African (AFR) AF: 0.000505 AC: 21 AN: 41558

American (AMR) AF: 0.00118 AC: 18 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.0186 AC: 198 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00415 AC: 282 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00347 Hom.: 5

Bravo AF: 0.00224

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00302

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		1.2
Mutation Taster		=92/8	polymorphism

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: rs41271969; hg19: chr1-162302846;