Variant rs121434581 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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. 14/20 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

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A4	NM_001042.3 linkuse as main transcript	c.1147G>A	p.Val383Ile	missense_variant	10/11	ENST00000317370.13	NP_001033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A4	ENST00000317370.13 linkuse as main transcript	c.1147G>A	p.Val383Ile	missense_variant	10/11	1	NM_001042.3	ENSP00000320935	P1	P14672-1

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

GnomAD3 exomes

AF:

0.00417

AC:

1049

AN:

251460

Hom.:

AF XY:

0.00432

AC XY:

587

AN XY:

135908

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 SAS exome

AF:

0.00268

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

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00470

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00253

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.00647

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.00404

AC:

615

AN:

152300

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00610

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00581

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

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	SLC2A4: BP4, BS2 -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Type 2 diabetes mellitus

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 01, 1995

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.088

T;T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-0.71

MutationTaster

Benign

0.71

A;A;A

PrimateAI

Benign

0.29

PROVEAN

Benign

0.13

N;.;N

REVEL

Uncertain

0.39

Sift

Benign

0.38

T;.;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.010

B;.;B

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

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.

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