12-117220188-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The NM_000620.5(NOS1):c.4057G>A(p.Val1353Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00129 in 1,613,978 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V1353V) has been classified as Benign.
Frequency
Consequence
NM_000620.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOS1 | NM_000620.5 | c.4057G>A | p.Val1353Ile | missense_variant | 27/29 | ENST00000317775.11 | |
NOS1 | NM_001204218.2 | c.4159G>A | p.Val1387Ile | missense_variant | 28/30 | ||
NOS1 | NM_001204213.2 | c.3049G>A | p.Val1017Ile | missense_variant | 26/28 | ||
NOS1 | NM_001204214.2 | c.3049G>A | p.Val1017Ile | missense_variant | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOS1 | ENST00000317775.11 | c.4057G>A | p.Val1353Ile | missense_variant | 27/29 | 1 | NM_000620.5 | P1 | |
NOS1 | ENST00000338101.8 | c.4159G>A | p.Val1387Ile | missense_variant | 27/29 | 5 | |||
NOS1 | ENST00000618760.4 | c.4159G>A | p.Val1387Ile | missense_variant | 28/30 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000874 AC: 133AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000977 AC: 244AN: 249704Hom.: 1 AF XY: 0.00104 AC XY: 141AN XY: 135262
GnomAD4 exome AF: 0.00134 AC: 1957AN: 1461636Hom.: 3 Cov.: 31 AF XY: 0.00137 AC XY: 998AN XY: 727140
GnomAD4 genome AF: 0.000866 AC: 132AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.000859 AC XY: 64AN XY: 74494
ClinVar
Submissions by phenotype
NOS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 19, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at