rs2235491

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A206V) has been classified as Uncertain significance.

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:11

Conservation

PhyloP100: 0.109

Publications

30 publications found

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 Gene-Disease associations (from GenCC):

arterial tortuosity syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp

SLC2A10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 139172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030777.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	NM_030777.4	MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 2 of 5	NP_110404.1	O95528

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 2 of 5	ENSP00000352216.2	O95528
SLC2A10	ENST00000862794.1		c.910G>A	p.Ala304Thr	missense	Exon 2 of 5	ENSP00000532853.1
SLC2A10	ENST00000862792.1		c.616G>A	p.Ala206Thr	missense	Exon 2 of 6	ENSP00000532851.1

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

GnomAD2 exomes

AF:

0.102

AC:

25546

AN:

250984

AF XY:

0.0953

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 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

African (AFR)

AF:

0.272

AC:

9102

AN:

33480

American (AMR)

AF:

0.221

AC:

9892

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

874

AN:

26134

East Asian (EAS)

AF:

0.0700

AC:

2780

AN:

39692

South Asian (SAS)

AF:

0.150

AC:

12933

AN:

86258

European-Finnish (FIN)

AF:

0.0710

AC:

3784

AN:

53310

Middle Eastern (MID)

AF:

0.109

AC:

627

AN:

5768

European-Non Finnish (NFE)

AF:

0.0409

AC:

45492

AN:

1111936

Other (OTH)

AF:

0.0753

AC:

4547

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

5877

11754

17631

23508

29385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2008

4016

6024

8032

10040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.122

AC:

18573

AN:

152174

Hom.:

1854

Cov.:

AF XY:

0.124

AC XY:

9213

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.263

AC:

10898

AN:

41490

American (AMR)

AF:

0.149

AC:

2283

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

136

AN:

3468

East Asian (EAS)

AF:

0.0889

AC:

460

AN:

5174

South Asian (SAS)

AF:

0.150

AC:

722

AN:

4826

European-Finnish (FIN)

AF:

0.0729

AC:

773

AN:

10610

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0444

AC:

3017

AN:

68006

Other (OTH)

AF:

0.106

AC:

224

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

749

1499

2248

2998

3747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0668

Hom.:

1251

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Arterial tortuosity syndrome (3)

Familial thoracic aortic aneurysm and aortic dissection (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.5

(source)

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

PhyloP100

0.11

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over