rs76315093

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030777.4(SLC2A10):​c.1288+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,605,492 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 6 hom., cov: 33)
Exomes 𝑓: 0.014 ( 190 hom. )

Consequence

SLC2A10
NM_030777.4 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.14
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 20-46726334-G-A is Benign according to our data. Variant chr20-46726334-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46726334-G-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00892 (1359/152286) while in subpopulation SAS AF= 0.0154 (74/4816). AF 95% confidence interval is 0.0133. There are 6 homozygotes in gnomad4. There are 628 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC2A10NM_030777.4 linkc.1288+10G>A intron_variant Intron 2 of 4 ENST00000359271.4 NP_110404.1 O95528

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC2A10ENST00000359271.4 linkc.1288+10G>A intron_variant Intron 2 of 4 1 NM_030777.4 ENSP00000352216.2 O95528

Frequencies

GnomAD3 genomes
AF:
0.00893
AC:
1359
AN:
152168
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00253
Gnomad AMI
AF:
0.0121
Gnomad AMR
AF:
0.00798
Gnomad ASJ
AF:
0.00865
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0154
Gnomad FIN
AF:
0.00273
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0141
Gnomad OTH
AF:
0.0125
GnomAD3 exomes
AF:
0.0103
AC:
2462
AN:
238094
Hom.:
25
AF XY:
0.0110
AC XY:
1433
AN XY:
129896
show subpopulations
Gnomad AFR exome
AF:
0.00233
Gnomad AMR exome
AF:
0.00557
Gnomad ASJ exome
AF:
0.00896
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0158
Gnomad FIN exome
AF:
0.00315
Gnomad NFE exome
AF:
0.0143
Gnomad OTH exome
AF:
0.0113
GnomAD4 exome
AF:
0.0142
AC:
20567
AN:
1453206
Hom.:
190
Cov.:
33
AF XY:
0.0143
AC XY:
10350
AN XY:
723216
show subpopulations
Gnomad4 AFR exome
AF:
0.00248
Gnomad4 AMR exome
AF:
0.00604
Gnomad4 ASJ exome
AF:
0.00857
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0168
Gnomad4 FIN exome
AF:
0.00418
Gnomad4 NFE exome
AF:
0.0158
Gnomad4 OTH exome
AF:
0.0121
GnomAD4 genome
AF:
0.00892
AC:
1359
AN:
152286
Hom.:
6
Cov.:
33
AF XY:
0.00843
AC XY:
628
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00253
Gnomad4 AMR
AF:
0.00797
Gnomad4 ASJ
AF:
0.00865
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0154
Gnomad4 FIN
AF:
0.00273
Gnomad4 NFE
AF:
0.0141
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.0117
Hom.:
1
Bravo
AF:
0.00900
Asia WGS
AF:
0.00549
AC:
19
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Arterial tortuosity syndrome Benign:5
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Oct 09, 2014
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

May 31, 2017
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 27, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:3
Feb 01, 2013
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jun 01, 2020
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: SLC2A10 c.1288+10G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: two predict the variant strengthens a cryptic 3' acceptor site; two predict the variant no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.01 in 238094 control chromosomes in the gnomAD database, including 25 homozygotes. The observed variant frequency is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Aortopathy phenotype (0.0016), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1288+10G>A in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign n=3, VUS n=1). Based on the evidence outlined above, the variant was classified as benign. -

Familial thoracic aortic aneurysm and aortic dissection Benign:2
Aug 30, 2015
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Apr 12, 2019
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
14
DANN
Benign
0.59

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: rs76315093; hg19: chr20-45354973; API