rs145994112
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000359271.4(SLC2A10):c.848C>A(p.Ala283Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,614,080 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A283G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000359271.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC2A10 | NM_030777.4 | c.848C>A | p.Ala283Asp | missense_variant | 2/5 | ENST00000359271.4 | NP_110404.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271.4 | c.848C>A | p.Ala283Asp | missense_variant | 2/5 | 1 | NM_030777.4 | ENSP00000352216 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251130Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135762
GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461846Hom.: 0 Cov.: 33 AF XY: 0.0000495 AC XY: 36AN XY: 727222
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74366
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 17, 2024 | PM3_supporting - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2022 | Reported in a female child with arterial tortuosity syndrome, atrial septal defect, inguinal hernia, and corneal thinning who also harbored an additional variant in the SLC2A10 gene (Hardin et al., 2018); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23142374, 28726533) - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2023 | The p.A283D variant (also known as c.848C>A), located in coding exon 2 of the SLC2A10 gene, results from a C to A substitution at nucleotide position 848. The alanine at codon 283 is replaced by aspartic acid, an amino acid with dissimilar properties. This alteration was reported as a compound heterozygote in a seven year old female with arterial tortuosity, atrial septal defect and corneal thinning (Hardin JS et al. Ophthalmic Genet, 2018 Jul;39:29-34). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Arterial tortuosity syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 22, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 283 of the SLC2A10 protein (p.Ala283Asp). This variant is present in population databases (rs145994112, gnomAD 0.008%). This missense change has been observed in individual(s) with arterial tortuosity syndrome (PMID: 28726533). ClinVar contains an entry for this variant (Variation ID: 213748). 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 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