rs35010541
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000330775.9(SLC37A4):c.1275C>T(p.Ser425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,790 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 33 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 66 hom. )
Consequence
SLC37A4
ENST00000330775.9 synonymous
ENST00000330775.9 synonymous
Scores
2
5
Clinical Significance
Conservation
PhyloP100: 0.723
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_addAF=-0.551845).
BP6
?
Variant 11-119024925-G-A is Benign according to our data. Variant chr11-119024925-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119024925-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.723 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1584/152366) while in subpopulation AFR AF= 0.0337 (1403/41582). AF 95% confidence interval is 0.0323. There are 33 homozygotes in gnomad4. There are 759 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC37A4 | NM_001164277.2 | c.1275C>T | p.Ser425= | synonymous_variant | 11/11 | ENST00000642844.3 | |
SLC37A4 | NM_001164279.2 | c.1056C>T | p.Ser352= | synonymous_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC37A4 | ENST00000330775.9 | c.1275C>T | p.Ser425= | synonymous_variant | 10/10 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0103 AC: 1571AN: 152248Hom.: 32 Cov.: 33
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GnomAD3 exomes AF: 0.00568 AC: 1412AN: 248560Hom.: 27 AF XY: 0.00609 AC XY: 822AN XY: 134884
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GnomAD4 exome AF: 0.00252 AC: 3678AN: 1461424Hom.: 66 Cov.: 32 AF XY: 0.00302 AC XY: 2198AN XY: 726960
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GnomAD4 genome ? AF: 0.0104 AC: 1584AN: 152366Hom.: 33 Cov.: 33 AF XY: 0.0102 AC XY: 759AN XY: 74504
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ESP6500AA
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glucose-6-phosphate transport defect Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 09, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 07, 2022 | - - |
Phosphate transport defect Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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