20-46709722-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_030777.4(SLC2A10):c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,545,498 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

SLC2A10
NM_030777.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.0900

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]

SLC2A10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 20-46709722-C-T is Benign according to our data. Variant chr20-46709722-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 139185.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=3, Likely_benign=2}.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00167 (255/152242) while in subpopulation AMR AF= 0.00287 (44/15306). AF 95% confidence interval is 0.0022. There are 2 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4 link	c.-15C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	ENST00000359271.4	NP_110404.1	O95528
SLC2A10	NM_030777.4 link	c.-15C>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000359271.4	NP_110404.1	O95528

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC2A10	ENST00000359271 link	c.-15C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	1	NM_030777.4	ENSP00000352216.2	O95528
SLC2A10	ENST00000359271 link	c.-15C>T	5_prime_UTR_variant	Exon 1 of 5	1	NM_030777.4	ENSP00000352216.2	O95528
SLC2A10	ENST00000486000 link	c.-15C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	3		ENSP00000478679.1	A0A087WUH5
SLC2A10	ENST00000486000 link	c.-15C>T	5_prime_UTR_variant	Exon 1 of 2	3		ENSP00000478679.1	A0A087WUH5

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00135

AC:

184

AN:

136752

Hom.:

AF XY:

0.00135

AC XY:

100

AN XY:

74220

show subpopulations

Gnomad AFR exome

AF:

0.000535

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.000125

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.0000659

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.00273

GnomAD4 exome

AF:

0.00182

AC:

2541

AN:

1393256

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1215

AN XY:

687248

show subpopulations

Gnomad4 AFR exome

AF:

0.000453

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000380

Gnomad4 FIN exome

AF:

0.0000839

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00167

AC:

255

AN:

152242

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00185

Asia WGS

AF:

0.000579

AC:

AN:

3470

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 30, 2024	Variant summary: SLC2A10 c.-15C>T is located in the untranslated mRNA region upstream of the initiation codon. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0018 in 1545498 control chromosomes in the gnomAD database (v4.1 dataset), including 7 homozygotes. The observed variant frequency is approximately 1.14 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Arterial Tortuosity Syndrome phenotype (0.0016), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.-15C>T in individuals affected with Arterial Tortuosity Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 139185). Based on the evidence outlined above, the variant was classified as benign. -

Arterial tortuosity syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Sep 26, 2019

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

SLC2A10: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over