chr11-119026079-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001164278.2(SLC37A4):āc.872C>Gā(p.Ala291Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,586,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001164278.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC37A4 | NM_001164278.2 | c.872C>G | p.Ala291Gly | missense_variant, splice_region_variant | Exon 9 of 12 | NP_001157750.1 | ||
SLC37A4 | NM_001164277.2 | c.872C>G | p.Ala291Gly | missense_variant, splice_region_variant | Exon 9 of 11 | NP_001157749.1 | ||
SLC37A4 | NM_001164280.2 | c.872C>G | p.Ala291Gly | missense_variant, splice_region_variant | Exon 7 of 9 | NP_001157752.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000546 AC: 83AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000192 AC: 40AN: 208402Hom.: 0 AF XY: 0.000197 AC XY: 22AN XY: 111666
GnomAD4 exome AF: 0.0000606 AC: 87AN: 1434508Hom.: 0 Cov.: 30 AF XY: 0.0000562 AC XY: 40AN XY: 711284
GnomAD4 genome AF: 0.000545 AC: 83AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000672 AC XY: 50AN XY: 74436
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Uncertain:2
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This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 291 of the SLC37A4 protein (p.Ala291Gly). This variant is present in population databases (rs200147602, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with SLC37A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 969047). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Uncertain:1Benign:1
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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Inborn genetic diseases Uncertain:1
The p.A291G variant (also known as c.872C>G), located in coding exon 6 of the SLC37A4 gene, results from a C to G substitution at nucleotide position 872. The alanine at codon 291 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Glucose-6-phosphate transport defect;C0342749:Phosphate transport defect;C5561986:Congenital disorder of glycosylation, type IIw Uncertain:1
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SLC37A4-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at