dbSNP rs201763908: NOSTRIN:p.Thr246Lys (chr2-168851286-C-A) – 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.737C>A(p.Thr246Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T246M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NOSTRIN
NM_001039724.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.532

Publications

0 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:

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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=0.14443836).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039724.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOSTRIN	NM_001039724.4	MANE Select	c.737C>A	p.Thr246Lys	missense	Exon 10 of 16	NP_001034813.2	Q8IVI9-1
NOSTRIN	NM_001171631.2		c.908C>A	p.Thr303Lys	missense	Exon 15 of 21	NP_001165102.1	Q8IVI9-4
NOSTRIN	NM_001171632.2		c.653C>A	p.Thr218Lys	missense	Exon 9 of 15	NP_001165103.1	Q8IVI9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOSTRIN	ENST00000317647.12	TSL:1 MANE Select	c.737C>A	p.Thr246Lys	missense	Exon 10 of 16	ENSP00000318921.7	Q8IVI9-1
NOSTRIN	ENST00000397209.6	TSL:1	c.653C>A	p.Thr218Lys	missense	Exon 9 of 15	ENSP00000380392.2	Q8IVI9-2
NOSTRIN	ENST00000397206.6	TSL:1	c.503C>A	p.Thr168Lys	missense	Exon 9 of 15	ENSP00000380390.2	Q8IVI9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

248514

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.0

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.76

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.53

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

REVEL

Benign

0.035

Sift

Benign

0.23

Sift4G

Benign

0.20

Polyphen

0.061

Vest4

0.39

MutPred

0.46

Gain of ubiquitination at T246 (P = 0.017)

MVP

0.47

MPC

0.12

ClinPred

0.61

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.091

gMVP

0.18

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over