2-168859617-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039724.4(NOSTRIN):ā€‹c.1159A>Gā€‹(p.Ile387Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

NOSTRIN
NM_001039724.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29265594).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOSTRINNM_001039724.4 linkuse as main transcriptc.1159A>G p.Ile387Val missense_variant 13/16 ENST00000317647.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOSTRINENST00000317647.12 linkuse as main transcriptc.1159A>G p.Ile387Val missense_variant 13/161 NM_001039724.4 P1Q8IVI9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249224
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135210
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461752
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000827
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 23, 2021The c.1330A>G (p.I444V) alteration is located in exon 18 (coding exon 14) of the NOSTRIN gene. This alteration results from a A to G substitution at nucleotide position 1330, causing the isoleucine (I) at amino acid position 444 to be replaced by a valine (V). 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
0.13
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
.;.;T;.;.;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
.;D;D;.;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.29
T;T;T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.6
.;.;M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.87
N;N;N;N;N;N
REVEL
Benign
0.076
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Benign
0.067
T;T;T;T;T;T
Polyphen
0.51, 0.90, 0.72
.;.;P;P;P;P
Vest4
0.51
MutPred
0.30
.;.;Loss of catalytic residue at I387 (P = 0.0623);.;.;.;
MVP
0.60
MPC
0.42
ClinPred
0.71
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.33
gMVP
0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752183055; hg19: chr2-169716127; API