rs111033638
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000155.4(GALT):c.18delC(p.Asp7fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GALT
NM_000155.4 frameshift
NM_000155.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.657
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 Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 79 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-34646720-AC-A is Pathogenic according to our data. Variant chr9-34646720-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 25113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.18delC | p.Asp7fs | frameshift_variant | 1/11 | ENST00000378842.8 | NP_000146.2 | |
GALT | NM_001258332.2 | c.-185delC | 5_prime_UTR_variant | 1/9 | NP_001245261.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.18delC | p.Asp7fs | frameshift_variant | 1/11 | 1 | NM_000155.4 | ENSP00000368119.4 | ||
ENSG00000258728 | ENST00000556278.1 | c.18delC | p.Asp7fs | frameshift_variant | 1/8 | 5 | ENSP00000451792.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461446Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727038
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32
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 24, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 20, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 25113). This variant is also known as T6fsdelC. This premature translational stop signal has been observed in individual(s) with clinical features of galactose-1-phosphate uridylyltransferase deficiency (PMID: 15775761). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp7Ilefs*43) in the GALT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 07, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at