7-151009552-G-T

Variant names:

• chr7-151009552-G-T
• NM_000603.5:c.2479G>T
• NOS3 p.Val827Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000603.5(NOS3):​c.2479G>T​(p.Val827Leu) 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. V827M) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOS3 NM_000603.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• Publications: 0 publications found

Genes affected

NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

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=0.16376218).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. 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
	NOS3	NM_000603.5	MANE Select	c.2479G>T	p.Val827Leu	missense	Exon 20 of 27	NP_000594.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.2479G>T	p.Val827Leu	missense	Exon 20 of 27	ENSP00000297494.3	P29474-1
	NOS3	ENST00000943234.1		c.2500G>T	p.Val834Leu	missense	Exon 19 of 26	ENSP00000613293.1
	NOS3	ENST00000908206.1		c.2479G>T	p.Val827Leu	missense	Exon 19 of 26	ENSP00000578265.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1391310 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 685926

African (AFR) AF: 0.00 AC: 0 AN: 31468

American (AMR) AF: 0.00 AC: 0 AN: 35450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25020

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.00 AC: 0 AN: 78882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4786

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077086

Other (OTH) AF: 0.00 AC: 0 AN: 57694

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.27	T
Sift4G	Benign	0.33	T
Varity_R		0.072
gMVP		0.35
Mutation Taster		=92/8	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-150706640;