9-34646609-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000450095.6(GALT):c.-298T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Consequence
GALT
ENST00000450095.6 5_prime_UTR
ENST00000450095.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.544
Genes affected
GALT (HGNC:4135): (galactose-1-phosphate uridylyltransferase) Galactose-1-phosphate uridyl transferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely the conversion of UDP-glucose + galactose-1-phosphate to glucose-1-phosphate + UDP-galactose. The absence of this enzyme results in classic galactosemia in humans and can be fatal in the newborn period if lactose is not removed from the diet. The pathophysiology of galactosemia has not been clearly defined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.19).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000450095.6 | c.-298T>G | 5_prime_UTR_variant | 1/9 | 2 | ENSP00000401956 | ||||
GALT | ENST00000605275.1 | n.209-68T>G | intron_variant, non_coding_transcript_variant | 3 | ||||||
GALT | ENST00000468099.2 | upstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.30e-7 AC: 1AN: 1370436Hom.: 0 Cov.: 22 AF XY: 0.00000146 AC XY: 1AN XY: 686028
GnomAD4 exome
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1
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1370436
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22
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1
AN XY:
686028
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 25, 2024 | Variant summary: GALT c.-96T>G is located in the untranscribed region upstream of the GALT gene region. The variant was absent in 31388 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.-96T>G has been reported in the literature as a compound heterozygous genotype together with a pathogenic variant in an individual affected with Galactosemia (Welling_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28065439, 31954591, 31845337). ClinVar contains an entry for this variant (Variation ID: 555856). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 29, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at