rs768345011
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030777.4(SLC2A10):c.1402G>A(p.Asp468Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D468G) has been classified as Uncertain significance.
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.1402G>A | p.Asp468Asn | missense_variant | 3/5 | ENST00000359271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271.4 | c.1402G>A | p.Asp468Asn | missense_variant | 3/5 | 1 | NM_030777.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251492Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135920
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727244
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2022 | The p.D468N variant (also known as c.1402G>A), located in coding exon 3 of the SLC2A10 gene, results from a G to A substitution at nucleotide position 1402. The aspartic acid at codon 468 is replaced by asparagine, an amino acid with highly 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2018 | A variant of uncertain significance has been identified in the SLC2A10 gene. Although the D468N variant has not been published as pathogenic or been reported as benign to our knowledge, it has been observed in three other individuals referred for Marfan/TAAD genetic testing at GeneDx, although a second variant in the SLC2A10 gene was not identified in any of these individuals. This variant is observed in 3/33,582 (0.01%) alleles from individuals of Latino ancestry in large population cohorts (Lek et al., 2016). The D468N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Nevertheless, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. - |
Arterial tortuosity syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 10, 2022 | 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. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 468 of the SLC2A10 protein (p.Asp468Asn). This variant is present in population databases (rs768345011, gnomAD 0.009%). 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: 213750). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at