rs2235491

Positions:

chr20-46725652-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030777.4(SLC2A10):c.616G>A(p.Ala206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,613,864 control chromosomes in the GnomAD database, including 6,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1854 hom., cov: 33)

Exomes 𝑓: 0.062 ( 5006 hom. )

Consequence

SLC2A10
NM_030777.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.109

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038325489).

BP6

Variant 20-46725652-G-A is Benign according to our data. Variant chr20-46725652-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46725652-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A10	NM_030777.4 linkuse as main transcript	c.616G>A	p.Ala206Thr	missense_variant	2/5	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4 linkuse as main transcript	c.616G>A	p.Ala206Thr	missense_variant	2/5	1	NM_030777.4	ENSP00000352216	P1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18537

AN:

152056

Hom.:

1845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.0885

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0729

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0443

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.102

AC:

25546

AN:

250984

Hom.:

2168

AF XY:

0.0953

AC XY:

12938

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.0329

Gnomad EAS exome

AF:

0.0838

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.0700

Gnomad NFE exome

AF:

0.0429

Gnomad OTH exome

AF:

0.0769

GnomAD4 exome

AF:

0.0616

AC:

90031

AN:

1461690

Hom.:

5006

Cov.:

AF XY:

0.0629

AC XY:

45711

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.272

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.0334

Gnomad4 EAS exome

AF:

0.0700

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.0710

Gnomad4 NFE exome

AF:

0.0409

Gnomad4 OTH exome

AF:

0.0753

GnomAD4 genome

AF:

0.122

AC:

18573

AN:

152174

Hom.:

1854

Cov.:

AF XY:

0.124

AC XY:

9213

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.0889

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.0729

Gnomad4 NFE

AF:

0.0444

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0546

Hom.:

612

Bravo

AF:

0.132

TwinsUK

AF:

0.0396

AC:

147

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.261

AC:

1151

ESP6500EA

AF:

0.0441

AC:

379

ExAC

AF:

0.101

AC:

12212

Asia WGS

AF:

0.147

AC:

511

AN:

3478

EpiCase

AF:

0.0449

EpiControl

AF:

0.0421

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Sep 24, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2012	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 06, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Ala206Thr in exon 2 of SLC2A10: This variant is not expected to have clinical significance because it has been identified in 26.1% (1151/4406) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs2235491). -

Arterial tortuosity syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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 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. -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2016

This alteration is classified as 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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.5

DANN

Benign

0.91

DEOGEN2

Benign

0.11

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.090

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

0.13

REVEL

Benign

0.10

Sift

Benign

0.58

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.016

MPC

0.065

ClinPred

0.00065

GERP RS

-0.60

Varity_R

0.029

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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