Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001042.3(SLC2A4):c.1147G>A(p.Val383Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,614,176 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 30 hom. )

Consequence

SLC2A4
NM_001042.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.253

Publications

21 publications found

Variant links:

Genes affected

SLC2A4 (HGNC:11009): (solute carrier family 2 member 4) This gene is a member of the solute carrier family 2 (facilitated glucose transporter) family and encodes a protein that functions as an insulin-regulated facilitative glucose transporter. In the absence of insulin, this integral membrane protein is sequestered within the cells of muscle and adipose tissue. Within minutes of insulin stimulation, the protein moves to the cell surface and begins to transport glucose across the cell membrane. Mutations in this gene have been associated with noninsulin-dependent diabetes mellitus (NIDDM). [provided by RefSeq, Jul 2008]

SLC2A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009615719).

BP6

Variant 17-7285729-G-A is Benign according to our data. Variant chr17-7285729-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 16089.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4	NM_001042.3	MANE Select	c.1147G>A	p.Val383Ile	missense	Exon 10 of 11	NP_001033.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC2A4	ENST00000317370.13	TSL:1 MANE Select	c.1147G>A	p.Val383Ile	missense	Exon 10 of 11	ENSP00000320935.8
SLC2A4	ENST00000572485.5	TSL:1	n.1208G>A		non_coding_transcript_exon	Exon 10 of 11	ENSP00000461086.1
SLC2A4	ENST00000571308.5	TSL:5	c.1147G>A	p.Val383Ile	missense	Exon 10 of 10	ENSP00000459864.1

Frequencies

GnomAD3 genomes

AF:

0.00404

AC:

615

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00610

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00417

AC:

1049

AN:

251460

AF XY:

0.00432

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00578

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00577

AC:

8430

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

4107

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

33476

American (AMR)

AF:

0.00470

AC:

210

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0131

AC:

342

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00253

AC:

218

AN:

86258

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00676

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00647

AC:

7199

AN:

1112002

Other (OTH)

AF:

0.00618

AC:

373

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

500

1000

1500

2000

2500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.00404

AC:

615

AN:

152300

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41550

American (AMR)

AF:

0.00529

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00248

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00610

AC:

415

AN:

68034

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00545

Hom.:

Bravo

AF:

0.00492

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00419

AC:

509

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00687

EpiControl

AF:

0.00682

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.088

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

M_CAP

Benign

0.020

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.71

PhyloP100

0.25

PrimateAI

Benign

0.29

PROVEAN

Benign

0.13

REVEL

Uncertain

0.39

Sift

Benign

0.38

Sift4G

Benign

0.53

Polyphen

0.010

Vest4

0.062

MVP

0.66

MPC

0.21

ClinPred

0.0088

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.055

gMVP

0.079

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001042.3:c.1147G>A

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over