dbSNP rs1174243545: NOSTRIN:p.Leu301Phe (chr2-168855399-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039724.4(NOSTRIN):c.903A>T(p.Leu301Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NOSTRIN
NM_001039724.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.333

Publications

2 publications found

Variant links:

Genes affected

NOSTRIN (HGNC:20203): (nitric oxide synthase trafficking) Nitric oxide (NO) is a potent mediator in biologic processes such as neurotransmission, inflammatory response, and vascular homeostasis. NOSTRIN binds the enzyme responsible for NO production, endothelial NO synthase (ENOS; MIM 163729), and triggers the translocation of ENOS from the plasma membrane to vesicle-like subcellular structures, thereby attenuating ENOS-dependent NO production.[supplied by OMIM, Apr 2004]

NOSTRIN links:

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

SPC25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16903886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOSTRIN	NM_001039724.4 link	c.903A>T	p.Leu301Phe	missense_variant	Exon 11 of 16	ENST00000317647.12	NP_001034813.2	Q8IVI9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOSTRIN	ENST00000317647.12 link	c.903A>T	p.Leu301Phe	missense_variant	Exon 11 of 16	1	NM_001039724.4	ENSP00000318921.7		Q8IVI9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248326

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459386

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.0000673

AC:

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39572

South Asian (SAS)

AF:

0.00

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110172

Other (OTH)

AF:

0.00

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 06, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1074A>T (p.L358F) alteration is located in exon 16 (coding exon 12) of the NOSTRIN gene. This alteration results from a A to T substitution at nucleotide position 1074, causing the leucine (L) at amino acid position 358 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0044

.;.;T;.;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.73

.;T;T;.;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.17

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

.;.;L;.;.;.

PhyloP100

0.33

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.099

Sift

Uncertain

0.025

D;D;D;D;D;D

Sift4G

Benign

0.067

T;T;T;T;T;T

Polyphen

0.69, 0.76

.;.;P;.;.;P

Vest4

0.25

MutPred

0.14

.;.;Loss of loop (P = 0.0374);.;.;.;

MVP

0.66

MPC

0.089

ClinPred

0.56

GERP RS

-0.78

Varity_R

0.066

gMVP

0.094

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over