Submissions for variant NM_000155.4(GALT):c.688-2A>C

gnomAD frequency: 0.00002  dbSNP: rs398123185

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078234	SCV000110072	pathogenic	not provided	2012-11-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781405	SCV000919407	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2017-09-26	criteria provided, single submitter	clinical testing	Variant summary: The GALT c.688-2A>C variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict the complete loss of a 3' splice acceptor site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 5/245194 control chromosomes at a frequency of 0.0000204, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALT variant (0.0028868). One clinical diagnostic laboratory/reputable database classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Invitae	RCV000781405	SCV003209764	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-03-26	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 92521). This variant has not been reported in the literature in individuals affected with GALT-related conditions. This variant is present in population databases (rs398123185, gnomAD 0.02%). This sequence change affects an acceptor splice site in intron 7 of the GALT gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367).