rs754355572
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030777.4(SLC2A10):āc.1423T>Gā(p.Leu475Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_030777.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A10 | NM_030777.4 | c.1423T>G | p.Leu475Val | missense_variant | 4/5 | ENST00000359271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271.4 | c.1423T>G | p.Leu475Val | missense_variant | 4/5 | 1 | NM_030777.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135870
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461472Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727056
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152330Hom.: 0 Cov.: 31 AF XY: 0.0000268 AC XY: 2AN XY: 74504
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2023 | The c.1423T>G (p.L475V) alteration is located in exon 4 (coding exon 4) of the SLC2A10 gene. This alteration results from a T to G substitution at nucleotide position 1423, causing the leucine (L) at amino acid position 475 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2013 | p.Leu475Val (TTG>GTG): c.1423 T>G in exon 4 of the SLC2A10 gene (NM_030777.3). The Leu475Val variant in the SLC2A10 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Leu475Val results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved in mammals. In silico analysis predicts possibly damaging to the protein structure/function. The NHLBI ESP Exome Variant Server reports Leu475Val was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby codons have been reported in association with arterial tortuosity syndrome. With the clinical and molecular information available at this time, we cannot definitively determine if Leu475Val is a disease-causing mutation or a rare benign variant. This variant was found in TAAD - |
Arterial tortuosity syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 475 of the SLC2A10 protein (p.Leu475Val). This variant is present in population databases (rs754355572, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC2A10-related conditions. ClinVar contains an entry for this variant (Variation ID: 213740). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC2A10 protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at