rs1555490611
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_020806.5(GPHN):c.1238C>T(p.Ala413Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_020806.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPHN | NM_020806.5 | c.1238C>T | p.Ala413Val | missense_variant, splice_region_variant | 13/23 | ENST00000478722.6 | NP_065857.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GPHN | ENST00000478722.6 | c.1238C>T | p.Ala413Val | missense_variant, splice_region_variant | 13/23 | 1 | NM_020806.5 | ENSP00000417901.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1447710Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1AN XY: 721254
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 18, 2017 | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GPHN-related disease. This sequence change replaces alanine with valine at codon 413 of the GPHN protein (p.Ala413Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at