rs141232328
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_000155.4(GALT):c.405G>A(p.Ser135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,058 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S135S) has been classified as Likely benign.
Frequency
Consequence
NM_000155.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.405G>A | p.Ser135= | synonymous_variant | 5/11 | ENST00000378842.8 | |
GALT | NM_001258332.2 | c.78G>A | p.Ser26= | synonymous_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.405G>A | p.Ser135= | synonymous_variant | 5/11 | 1 | NM_000155.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251490Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461890Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727244
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 03, 2023 | The GALT c.405G>A, p.Ser135Ser variant (rs141232328), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 281069). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The variant is a synonymous substitution at a weakly conserved nucleotide and computational analyses (Alamut Visual Plus v.1.5.1) predict that this variant may impact splicing by creating a novel cryptic acceptor splice site. Due to limited information, the clinical significance of this variant is uncertain at this time. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change affects codon 135 of the GALT mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GALT protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with galactosemia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 281069). 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. - |
Galactosemia Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 14, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 25, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at