rs121908975
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_001164278.2(SLC37A4):c.1129G>T(p.Glu377*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_001164278.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC37A4 | NM_001164278.2 | c.1129G>T | p.Glu377* | stop_gained | Exon 11 of 12 | NP_001157750.1 | ||
SLC37A4 | NM_001164277.2 | c.1063G>T | p.Glu355* | stop_gained | Exon 10 of 11 | NP_001157749.1 | ||
SLC37A4 | NM_001164280.2 | c.1063G>T | p.Glu355* | stop_gained | Exon 8 of 9 | NP_001157752.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460928Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726692
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Pathogenic:5
Variant summary: SLC37A4 c.1063G>T (p.Glu355X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 247192 control chromosomes. c.1063G>T has been reported in the literature in individuals affected with Glycogen Storage Disease Type Ib (example, Gerin_1997, Chou_2002). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic. -
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This premature translational stop signal has been observed in individual(s) with glycogen storage disease type Ib (PMID: 9428641, 11949931). 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: 6922). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Glu355*) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC37A4 are known to be pathogenic (PMID: 9758626, 10940311). This variant is not present in population databases (gnomAD no frequency). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at