7-150993910-C-T

Variant names:

• chr7-150993910-C-T
• NM_000603.5:c.107C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000603.5(NOS3):​c.107C>T​(p.Pro36Leu) 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. 13/21 in silico tools predict 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: 33)
• Consequence: NOS3 NM_000603.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090937674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.107C>T	p.Pro36Leu	missense_variant	Exon 2 of 27	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.107C>T	p.Pro36Leu	missense_variant	Exon 1 of 14		NP_001153583.1
NOS3	NM_001160110.1	c.107C>T	p.Pro36Leu	missense_variant	Exon 1 of 14		NP_001153582.1
NOS3	NM_001160109.2	c.107C>T	p.Pro36Leu	missense_variant	Exon 1 of 14		NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.107C>T	p.Pro36Leu	missense_variant	Exon 2 of 27	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000484524.5	c.107C>T	p.Pro36Leu	missense_variant	Exon 1 of 14	1		ENSP00000420215.1
NOS3	ENST00000467517.1	c.107C>T	p.Pro36Leu	missense_variant	Exon 1 of 14	1		ENSP00000420551.1
NOS3	ENST00000461406.5	c.-148-1293C>T		intron_variant	Intron 1 of 23	2		ENSP00000417143.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107C>T (p.P36L) alteration is located in exon 2 (coding exon 1) of the NOS3 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the proline (P) at amino acid position 36 to be replaced by a leucine (L). 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	0.082
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.68	N;N;N
REVEL	Benign	0.068
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.32	T;D;D
Polyphen		0.0	B;.;.
Vest4		0.14
MutPred		0.13		Loss of glycosylation at P36 (P = 0.0258);Loss of glycosylation at P36 (P = 0.0258);Loss of glycosylation at P36 (P = 0.0258);
MVP		0.42
MPC		0.066
ClinPred		0.077	T
GERP RS		3.3
Varity_R		0.16
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150690998;