rs1555887907

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_030777.4(SLC2A10):​c.397G>A​(p.Gly133Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLC2A10
NM_030777.4 missense

Scores

15
3
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.98
Variant links:
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 Likely_pathogenic. Variant got 8 ACMG points.

PM1
In a topological_domain Cytoplasmic (size 6) in uniprot entity GTR10_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_030777.4
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC2A10NM_030777.4 linkc.397G>A p.Gly133Arg missense_variant Exon 2 of 5 ENST00000359271.4 NP_110404.1 O95528

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC2A10ENST00000359271.4 linkc.397G>A p.Gly133Arg missense_variant Exon 2 of 5 1 NM_030777.4 ENSP00000352216.2 O95528
SLC2A10ENST00000611837.1 linkn.549G>A non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Arterial tortuosity syndrome Uncertain:1
Feb 19, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces glycine with arginine at codon 133 of the SLC2A10 protein (p.Gly133Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SLC2A10-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.42
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.66
D
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.92
D
M_CAP
Pathogenic
0.38
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
0.96
D
MutationAssessor
Pathogenic
4.7
H
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-7.7
D
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.89
MutPred
0.95
Loss of catalytic residue at V134 (P = 0.0248);
MVP
0.96
MPC
0.43
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.96
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555887907; hg19: chr20-45354072; COSMIC: COSV63714529; API