2-168856757-C-T

Variant names:

• chr2-168856757-C-T
• rs200081205
• NM_001039724.4:c.1032C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001039724.4(NOSTRIN):​c.1032C>T​(p.Asp344Asp) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOSTRIN NM_001039724.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.156 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	NM_001039724.4	MANE Select	c.1032C>T	p.Asp344Asp	synonymous	Exon 12 of 16	NP_001034813.2	Q8IVI9-1
	NOSTRIN	NM_001171631.2		c.1203C>T	p.Asp401Asp	synonymous	Exon 17 of 21	NP_001165102.1	Q8IVI9-4
	NOSTRIN	NM_001171632.2		c.948C>T	p.Asp316Asp	synonymous	Exon 11 of 15	NP_001165103.1	Q8IVI9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	ENST00000317647.12	TSL:1 MANE Select	c.1032C>T	p.Asp344Asp	synonymous	Exon 12 of 16	ENSP00000318921.7	Q8IVI9-1
	NOSTRIN	ENST00000397209.6	TSL:1	c.948C>T	p.Asp316Asp	synonymous	Exon 11 of 15	ENSP00000380392.2	Q8IVI9-2
	NOSTRIN	ENST00000397206.6	TSL:1	c.798C>T	p.Asp266Asp	synonymous	Exon 11 of 15	ENSP00000380390.2	Q8IVI9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.8
DANN	Benign	0.81
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs200081205; hg19: chr2-169713267;