12-117218073-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000620.5(NOS1):āc.4262T>Cā(p.Ile1421Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000620.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOS1 | NM_000620.5 | c.4262T>C | p.Ile1421Thr | missense_variant | Exon 28 of 29 | ENST00000317775.11 | NP_000611.1 | |
NOS1 | NM_001204218.2 | c.4364T>C | p.Ile1455Thr | missense_variant | Exon 29 of 30 | NP_001191147.1 | ||
NOS1 | NM_001204213.2 | c.3254T>C | p.Ile1085Thr | missense_variant | Exon 27 of 28 | NP_001191142.1 | ||
NOS1 | NM_001204214.2 | c.3254T>C | p.Ile1085Thr | missense_variant | Exon 27 of 28 | NP_001191143.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOS1 | ENST00000317775.11 | c.4262T>C | p.Ile1421Thr | missense_variant | Exon 28 of 29 | 1 | NM_000620.5 | ENSP00000320758.6 | ||
NOS1 | ENST00000338101.8 | c.4364T>C | p.Ile1455Thr | missense_variant | Exon 28 of 29 | 5 | ENSP00000337459.4 | |||
NOS1 | ENST00000618760.4 | c.4364T>C | p.Ile1455Thr | missense_variant | Exon 29 of 30 | 5 | ENSP00000477999.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249496Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135354
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727192
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.4364T>C (p.I1455T) alteration is located in exon 29 (coding exon 28) of the NOS1 gene. This alteration results from a T to C substitution at nucleotide position 4364, causing the isoleucine (I) at amino acid position 1455 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at