rs80358230
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 14P and 1B. PM1PP3_StrongPP5_Very_StrongBS1_Supporting
The NM_030777.4(SLC2A10):āc.243C>Gā(p.Ser81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,830 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000011 ( 2 hom. )
Consequence
SLC2A10
NM_030777.4 missense
NM_030777.4 missense
Scores
8
10
1
Clinical Significance
Conservation
PhyloP100: 3.13
Genes affected
SLC2A10 (HGNC:13444): (solute carrier family 2 member 10) This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PM1
?
In a transmembrane_region Helical; Name=3 (size 20) in uniprot entity GTR10_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_030777.4
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.989
PP5
?
Variant 20-46725279-C-G is Pathogenic according to our data. Variant chr20-46725279-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 4588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46725279-C-G is described in Lovd as [Pathogenic].
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000109 (16/1461830) while in subpopulation MID AF= 0.00278 (16/5754). AF 95% confidence interval is 0.00174. There are 2 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A10 | NM_030777.4 | c.243C>G | p.Ser81Arg | missense_variant | 2/5 | ENST00000359271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271.4 | c.243C>G | p.Ser81Arg | missense_variant | 2/5 | 1 | NM_030777.4 | P1 | |
SLC2A10 | ENST00000611837.1 | n.395C>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461830Hom.: 2 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727216
GnomAD4 exome
AF:
AC:
16
AN:
1461830
Hom.:
Cov.:
33
AF XY:
AC XY:
7
AN XY:
727216
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:8Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Arterial tortuosity syndrome Pathogenic:6Other:1
Likely pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Sep 26, 2019 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 15, 2020 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Provincial Medical Genetics Program of British Columbia, University of British Columbia | Jan 01, 2022 | - - |
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2008 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 16, 2023 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 81 of the SLC2A10 protein (p.Ser81Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with arterial tortuosity syndrome (PMID: 16550171, 18565096). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4588). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC2A10 protein function. For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 17, 2022 | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31203799, 34426522, 16550171, 24123366, 25373504, 30090112, 18774132, 31625567, 35302653, 36011280, 18565096) - |
SLC2A10-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 05, 2023 | The SLC2A10 c.243C>G variant is predicted to result in the amino acid substitution p.Ser81Arg. This variant has been reported to be pathogenic for arterial tortuosity syndrome (Coucke et al. 2006. PubMed ID: 16550171; Rodriguez-Flores et al. 2014. PubMed ID: 24123366; Faiyaz-Ul-Haque et al. 2009. PubMed ID: 18774132). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of methylation at S81 (P = 0.0157);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at