chr20-46709737-A-G

Variant summary

Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5

The NM_030777.4(SLC2A10):ā€‹c.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

Scores

5
4
7

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1

Conservation

PhyloP100: 2.65
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 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
SLC2A10NM_030777.4 linkuse as main transcriptc.1A>G p.Met1? start_lost 1/5 ENST00000359271.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC2A10ENST00000359271.4 linkuse as main transcriptc.1A>G p.Met1? start_lost 1/51 NM_030777.4 P1
SLC2A10ENST00000486000.2 linkuse as main transcriptc.1A>G p.Met1? start_lost 1/23

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000144
AC:
2
AN:
138642
Hom.:
0
AF XY:
0.0000133
AC XY:
1
AN XY:
75202
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000412
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000207
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000287
AC:
4
AN:
1394556
Hom.:
0
Cov.:
30
AF XY:
0.00000291
AC XY:
2
AN XY:
687920
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000281
Gnomad4 ASJ exome
AF:
0.0000399
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000186
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000312
Hom.:
0

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 submitterclinical testingCenter for Genomic Medicine, King Faisal Specialist Hospital and Research CenterMar 26, 2024- -
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 14, 2022For 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.90
D;.
M_CAP
Pathogenic
0.99
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Benign
-0.62
T
MutationTaster
Benign
1.0
D
PROVEAN
Benign
-0.95
N;.
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;.
Polyphen
0.0030
B;.
Vest4
0.78
MutPred
0.99
Gain of catalytic residue at M1 (P = 0.0537);Gain of catalytic residue at M1 (P = 0.0537);
MVP
0.77
ClinPred
0.95
D
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.92
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1355346296; hg19: chr20-45338376; API