chr20-46709737-A-G
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Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_030777.4(SLC2A10):āc.1A>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,394,556 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).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000029 ( 0 hom. )
Consequence
SLC2A10
NM_030777.4 start_lost
NM_030777.4 start_lost
Scores
5
4
7
Clinical Significance
Conservation
PhyloP100: 2.65
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.
PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in NM_030777.4 (SLC2A10) was described as [Likely_pathogenic] in ClinVar as 3319431
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 20-46709737-A-G is Pathogenic according to our data. Variant chr20-46709737-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2017181.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A10 | NM_030777.4 | c.1A>G | p.Met1? | start_lost | 1/5 | ENST00000359271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271.4 | c.1A>G | p.Met1? | start_lost | 1/5 | 1 | NM_030777.4 | P1 | |
SLC2A10 | ENST00000486000.2 | c.1A>G | p.Met1? | start_lost | 1/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000144 AC: 2AN: 138642Hom.: 0 AF XY: 0.0000133 AC XY: 1AN XY: 75202
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GnomAD4 exome AF: 0.00000287 AC: 4AN: 1394556Hom.: 0 Cov.: 30 AF XY: 0.00000291 AC XY: 2AN XY: 687920
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Arterial tortuosity syndrome Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 14, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SLC2A10 protein in which other variant(s) (p.Ser81Arg) have been determined to be pathogenic (PMID: 16550171, 18565096). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with SLC2A10-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects the initiator methionine of the SLC2A10 mRNA. The next in-frame methionine is located at codon 117. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;.
Polyphen
B;.
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0537);Gain of catalytic residue at M1 (P = 0.0537);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at