rs1057338763
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_020806.5(GPHN):c.381G>A(p.Met127Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,593,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M127T) has been classified as Uncertain significance.
Frequency
Consequence
NM_020806.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPHN | NM_020806.5 | c.381G>A | p.Met127Ile | missense_variant | 5/23 | ENST00000478722.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPHN | ENST00000478722.6 | c.381G>A | p.Met127Ile | missense_variant | 5/23 | 1 | NM_020806.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151922Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250246Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135246
GnomAD4 exome AF: 0.0000479 AC: 69AN: 1441430Hom.: 0 Cov.: 27 AF XY: 0.0000459 AC XY: 33AN XY: 718392
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151922Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74190
ClinVar
Submissions by phenotype
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GPHN protein function. ClinVar contains an entry for this variant (Variation ID: 534551). This variant has not been reported in the literature in individuals affected with GPHN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 127 of the GPHN protein (p.Met127Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at