rs111033732
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000155.4(GALT):c.564+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,614,072 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
GALT
NM_000155.4 intron
NM_000155.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.540
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 Benign. Variant got -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 9-34648186-G-A is Benign according to our data. Variant chr9-34648186-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 25216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.564+15G>A | intron_variant | ENST00000378842.8 | |||
GALT | NM_001258332.2 | c.237+15G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.564+15G>A | intron_variant | 1 | NM_000155.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000617 AC: 155AN: 251418Hom.: 0 AF XY: 0.000471 AC XY: 64AN XY: 135902
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GnomAD4 exome AF: 0.000120 AC: 176AN: 1461774Hom.: 0 Cov.: 33 AF XY: 0.000100 AC XY: 73AN XY: 727194
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GnomAD4 genome AF: 0.000144 AC: 22AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 25, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 19, 2016 | Variant summary: The GALT c.564+15G>A variant affects a non-conserved intronic nucleotide not widely known to impact normal splicing. Mutation Taster predicts a benign outcome for this variant, and 4/5 Alamut algorithms predict no change to the splice donor site, however these in silico predictions have not been verified with functional studies. This variant is found in 48/121384 control chromosomes at a frequency of 0.0003954, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0028868). This variant has been cited in one Hispanic classic GALT patient (Yang_HM_2002), authors did not provide co-segregation data, and the allele frequency in Latinos from the ExAC project is 2-fold greater (48/11576 alleles; 0.00415), thus this variant is likely a benign polymorphism found in Latinos. Additionally, multiple clinical labs/databases classify the variant as benign/likely benign without providing evidence to independently evaluate. Taken together, the variant was classified as Likely Benign until additional information becomes available. - |
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at