chr1-162367380-G-C

Variant names:

• chr1-162367380-G-C
• rs115433966
• NM_014697.3:c.1434G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014697.3(NOS1AP):​c.1434G>C​(p.Ser478Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000628 in 1,608,352 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: NOS1AP NM_014697.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.552
• Publications: 0 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)

ENSG00000254706 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-162367380-G-C is Benign according to our data. Variant chr1-162367380-G-C is described in ClinVar as Benign. ClinVar VariationId is 496431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.552 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.1434G>C	p.Ser478Ser	synonymous	Exon 10 of 10	NP_055512.1
	NOS1AP	NM_001164757.2		c.1419G>C	p.Ser473Ser	synonymous	Exon 10 of 10	NP_001158229.1
	NOS1AP	NM_001126060.2		c.549G>C	p.Ser183Ser	synonymous	Exon 2 of 2	NP_001119532.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.1434G>C	p.Ser478Ser	synonymous	Exon 10 of 10	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.1419G>C	p.Ser473Ser	synonymous	Exon 10 of 10	ENSP00000431586.1
	NOS1AP	ENST00000493151.1	TSL:1	c.549G>C	p.Ser183Ser	synonymous	Exon 2 of 2	ENSP00000434988.1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 540 AN: 152236 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000774 AC: 184 AN: 237750 AF XY: 0.000579

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000237

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000323 AC: 470 AN: 1455998 Hom.: 2 Cov.: 31 AF XY: 0.000300 AC XY: 217 AN XY: 723806

African (AFR) AF: 0.0120 AC: 401 AN: 33384

American (AMR) AF: 0.000339 AC: 15 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39502

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51996

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1109412

Other (OTH) AF: 0.000682 AC: 41 AN: 60102

GnomAD4 genome AF: 0.00354 AC: 540 AN: 152354 Hom.: 1 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74504

African (AFR) AF: 0.0126 AC: 525 AN: 41588

American (AMR) AF: 0.000523 AC: 8 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000248 Hom.: 0

Bravo AF: 0.00388

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		-0.55
PromoterAI		0.085	Neutral
Mutation Taster		=99/1	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: rs115433966; hg19: chr1-162337170;