ClinVar

Description

The GALT c.289_291delAAC variant is predicted to result in an in-frame deletion (p.Asn97del). This variant has been reported in the homozygous state or heterozygous state with a second pathogenic GALT variant in individuals with galactosemia (Boutron et al. 2012. PubMed ID: 22944367; Schadewaldt et al. 2014. PubMed ID: 25268296; Garcia et al. 2016. PubMed ID: 27176039). It was also reported in a cohort of Swedish galactosemia patients, although no additional clinical or genetic information was reported about the patient in that cohort (Ohlsson et al. 2019. PubMed ID: 31194895). The p.Asn97 amino acid is involved in Hydrogen bonding with UDP-alpha-D-glucose, and disruption of this amino acid is predicted to impact both the enzyme active site and intersubunit interactions (Boutron et al. 2012. PubMed ID: 22944367; https://www.uniprot.org/uniprotkb/P07902). Several substitutions of the p.Asn97 amino acid (p.Asn97Asp, p.Asn97Ser, p.Asn97Ile) have been reported in patients with galactosemia (Boutron et al. 2012. PubMed ID: 22944367; Shin. 2004. PubMed ID: 15633893; ClinVar ID #811178). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In summary, this variant is interpreted as pathogenic.