rs76315093

Variant names:

• chr20-46726334-G-A
• rs76315093
• NM_030777.4:c.1288+10G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 1.14

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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.1288+10G>A		intron_variant	Intron 2 of 4	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4	c.1288+10G>A		intron_variant	Intron 2 of 4	1	NM_030777.4	ENSP00000352216.2

Frequencies

GnomAD3 genomes AF: 0.00893 AC: 1359 AN: 152168 Hom.: 6 Cov.: 33

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

GnomAD2 exomes AF: 0.0103 AC: 2462 AN: 238094 AF XY: 0.0110

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 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

Gnomad4 AFR exome AF: 0.00248 AC: 83 AN: 33476

Gnomad4 AMR exome AF: 0.00604 AC: 270 AN: 44714

Gnomad4 ASJ exome AF: 0.00857 AC: 224 AN: 26134

Gnomad4 EAS exome AF: 0.0000504 AC: 2 AN: 39698

Gnomad4 SAS exome AF: 0.0168 AC: 1445 AN: 86228

Gnomad4 FIN exome AF: 0.00418 AC: 188 AN: 44946

Gnomad4 NFE exome AF: 0.0158 AC: 17573 AN: 1111920

Gnomad4 Remaining exome AF: 0.0121 AC: 728 AN: 60324

GnomAD4 genome AF: 0.00892 AC: 1359 AN: 152286 Hom.: 6 Cov.: 33 AF XY: 0.00843 AC XY: 628 AN XY: 74478

Gnomad4 AFR AF: 0.00253 AC: 0.00252744 AN: 0.00252744

Gnomad4 AMR AF: 0.00797 AC: 0.00796865 AN: 0.00796865

Gnomad4 ASJ AF: 0.00865 AC: 0.00864553 AN: 0.00864553

Gnomad4 EAS AF: 0.000193 AC: 0.00019305 AN: 0.00019305

Gnomad4 SAS AF: 0.0154 AC: 0.0153654 AN: 0.0153654

Gnomad4 FIN AF: 0.00273 AC: 0.00272813 AN: 0.00272813

Gnomad4 NFE AF: 0.0141 AC: 0.014069 AN: 0.014069

Gnomad4 OTH AF: 0.0123 AC: 0.012334 AN: 0.012334

Alfa AF: 0.0109 Hom.: 3

Bravo AF: 0.00900

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Arterial tortuosity syndrome Benign:5

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. -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified Benign:4

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. -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs76315093; hg19: chr20-45354973;