rs1689150656

Variant names:

• chr2-168856771-T-A
• rs1689150656
• NM_001039724.4:c.1046T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-168856771-T-A
• chr2-168856771-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001039724.4(NOSTRIN):​c.1046T>A​(p.Met349Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. M349T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOSTRIN NM_001039724.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.27
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOSTRIN	NM_001039724.4	c.1046T>A	p.Met349Lys	missense_variant	Exon 12 of 16	ENST00000317647.12	NP_001034813.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOSTRIN	ENST00000317647.12	c.1046T>A	p.Met349Lys	missense_variant	Exon 12 of 16	1	NM_001039724.4	ENSP00000318921.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.038	.;.;T;.;.;.
Eigen	Benign	-0.076
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	.;D;D;.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.56	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;.;M;.;.;.
PhyloP100		5.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D;D
REVEL	Benign	0.10
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Polyphen		0.0030	.;.;B;B;B;B
Vest4		0.70
MutPred		0.41		.;.;Gain of ubiquitination at M349 (P = 0.0014);.;.;.;
MVP		0.61
MPC		0.23
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.79
gMVP		0.66
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1689150656; hg19: chr2-169713281;