9-34647529-A-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000155.4(GALT):c.290A>T(p.Asn97Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N97D) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000155.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.290A>T | p.Asn97Ile | missense_variant | 3/11 | ENST00000378842.8 | |
GALT | NM_001258332.2 | c.50+271A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.290A>T | p.Asn97Ile | missense_variant | 3/11 | 1 | NM_000155.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2018 | The GALT c.290A>T; p.Asn97Ile variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The asparagine at codon 97 is highly conserved, is involved in ligand binding (Boutron 2012), and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Other variants at this codon (c.290A>G, p.Asn97Ser; c.289A>G; p.Asn97Asp) have been reported in individuals with galactosemia and are considered pathogenic (Boutron 2012, Shin 2004). Based on available information, the p.Asn97Ile variant is considered to be likely pathogenic. References: Boutron A et al. Mutation spectrum in the French cohort of galactosemic patients and structural simulation of 27 novel missense variations. Mol Genet Metab. 2012 Nov;107(3):438-47. Shin YS et al. Molecular and biochemical basis for variants and deficiency of GALT: report of 4 novel mutations. Bratisl Lek Listy. 2004;105(9):315-7. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at