rs34203644
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001164278.2(SLC37A4):c.593A>T(p.Asn198Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00492 in 1,613,926 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N198S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001164278.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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SLC37A4 | NM_001164278.2 | c.593A>T | p.Asn198Ile | missense_variant | Exon 6 of 12 | NP_001157750.1 | ||
SLC37A4 | NM_001164277.2 | c.593A>T | p.Asn198Ile | missense_variant | Exon 6 of 11 | NP_001157749.1 | ||
SLC37A4 | NM_001164280.2 | c.593A>T | p.Asn198Ile | missense_variant | Exon 4 of 9 | NP_001157752.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00388 AC: 590AN: 152188Hom.: 4 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00363 AC: 903AN: 249060 AF XY: 0.00366 show subpopulations
GnomAD4 exome AF: 0.00503 AC: 7349AN: 1461620Hom.: 23 Cov.: 32 AF XY: 0.00493 AC XY: 3581AN XY: 727092 show subpopulations
GnomAD4 genome AF: 0.00387 AC: 590AN: 152306Hom.: 4 Cov.: 33 AF XY: 0.00369 AC XY: 275AN XY: 74492 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:8
SLC37A4: BS2 -
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Variant summary:The c.593A>T in SLC37A4 gene is a missense change that alters a conserved nucleotide and 2/4 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.36% exclusively in individuals of European descent (0.53%), including 2 homozygous occurrences. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in SLC37A4 gene (0.12%). The variant of interest has been reported in three GSD1b patients (Zappu_2010) who also carried a splice-site mutation in homozygous state, strongly suggesting for benign outcome. In functional studies the variant had normal G6P transport activity (Chen, 2010). In addition, the variant has been reported as Benign/Polymorphism by a clinical laboratory and published reports (Zappu, 2010) Taking together, the variant has been classified as Benign. -
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not specified Benign:2
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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. -
Glucose-6-phosphate transport defect Benign:2
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at