rs121908975
Variant names:
Your query was ambiguous. Multiple possible variants found:
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
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SLC37A4
NM_001164278.2 stop_gained
NM_001164278.2 stop_gained
Scores
3
2
Clinical Significance
Conservation
PhyloP100: 7.37
Genes affected
SLC37A4 (HGNC:4061): (solute carrier family 37 member 4) This gene regulates glucose-6-phosphate transport from the cytoplasm to the lumen of the endoplasmic reticulum, in order to maintain glucose homeostasis. It also plays a role in ATP-mediated calcium sequestration in the lumen of the endoplasmic reticulum. Mutations in this gene have been associated with various forms of glycogen storage disease. Alternative splicing in this gene results in multiple transcript variants.[provided by RefSeq, Aug 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.167 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-119025251-C-A is Pathogenic according to our data. Variant chr11-119025251-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 6922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
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
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 exome
AF:
AC:
1
AN:
1460928
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
726692
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glucose-6-phosphate transport defect Pathogenic:5
| Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 21, 2021 | 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. - |
| Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 15, 1997 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 01, 2022 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 10, 2020 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 04, 2022 | 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
FATHMM_MKL
Pathogenic
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at