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GeneBe

rs1799983

chr7-150999023-T-Achr7-150999023-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM2_SupportingBP4_Strong

The NM_000603.5(NOS3):c.894T>A(p.Asp298Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151882 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Consequence

NOS3
NM_000603.5 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

Links

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.00000658 (1/151882) while in subpopulation NFE AF= 0.0000147 (1/67946). AF 95% confidence interval is 0. There are 0 homozygotes in gnomad. There are 0 alleles in male gnomad subpopulation. Median coverage is 30. This position pass quality control queck.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.03785497).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOS3NM_000603.5 linkuse as main transcriptc.894T>A p.Asp298Glu missense_variant 8/27 ENST00000297494.8
NOS3NM_001160111.1 linkuse as main transcriptc.894T>A p.Asp298Glu missense_variant 7/14
NOS3NM_001160110.1 linkuse as main transcriptc.894T>A p.Asp298Glu missense_variant 7/14
NOS3NM_001160109.2 linkuse as main transcriptc.894T>A p.Asp298Glu missense_variant 7/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOS3ENST00000297494.8 linkuse as main transcriptc.894T>A p.Asp298Glu missense_variant 8/271 NM_000603.5 P1P29474-1
NOS3ENST00000484524.5 linkuse as main transcriptc.894T>A p.Asp298Glu missense_variant 7/141 P29474-2
NOS3ENST00000467517.1 linkuse as main transcriptc.894T>A p.Asp298Glu missense_variant 7/141 P29474-3
NOS3ENST00000461406.5 linkuse as main transcriptc.276T>A p.Asp92Glu missense_variant 5/242

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151882
Hom.:
0
Cov.:
30
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
Cadd
Benign
9.8
Dann
Benign
0.24
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.18
T;T;T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.038
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.90
N;N;N;N
REVEL
Benign
0.053
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
.;B;.;.
Vest4
0.048
MutPred
0.43
.;Loss of sheet (P = 0.0817);.;.;
MVP
0.16
MPC
0.061
ClinPred
0.032
T
GERP RS
1.0
Varity_R
0.013
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1799983; hg19: chr7-150696111;