rs5400

Positions:

chr3-171014511-G-A

Variant summary

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

The NM_000340.2(SLC2A2):c.329C>T(p.Thr110Ile) variant causes a missense change. The variant allele was found at a frequency of 0.143 in 1,613,530 control chromosomes in the GnomAD database, including 21,251 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 Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5454 hom., cov: 32)

Exomes 𝑓: 0.13 ( 15797 hom. )

Consequence

SLC2A2
NM_000340.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 7.13

Variant links:

Genes affected

SLC2A2 (HGNC:11006): (solute carrier family 2 member 2) This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

SLC2A2 links:

(HGNC:):

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=0.002820909).

BP6

Variant 3-171014511-G-A is Benign according to our data. Variant chr3-171014511-G-A is described in ClinVar as [Benign]. Clinvar id is 130349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-171014511-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A2	NM_000340.2 linkuse as main transcript	c.329C>T	p.Thr110Ile	missense_variant	3/11	ENST00000314251.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A2	ENST00000314251.8 linkuse as main transcript	c.329C>T	p.Thr110Ile	missense_variant	3/11	1	NM_000340.2	P1	P11168-1
	ENST00000655926.1 linkuse as main transcript	n.291+19486G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33796

AN:

151980

Hom.:

5439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.00925

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.147

AC:

36820

AN:

251322

Hom.:

3807

AF XY:

0.144

AC XY:

19624

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.00555

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.135

AC:

196835

AN:

1461432

Hom.:

15797

Cov.:

AF XY:

0.135

AC XY:

98005

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.0143

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.223

AC:

33852

AN:

152098

Hom.:

5454

Cov.:

AF XY:

0.220

AC XY:

16398

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.458

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.00927

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.148

Hom.:

5302

Bravo

AF:

0.234

TwinsUK

AF:

0.129

AC:

477

ALSPAC

AF:

0.127

AC:

489

ESP6500AA

AF:

0.447

AC:

1970

ESP6500EA

AF:

0.133

AC:

1147

ExAC

AF:

0.154

AC:

18691

Asia WGS

AF:

0.110

AC:

387

AN:

3478

EpiCase

AF:

0.142

EpiControl

AF:

0.142

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 14, 2015	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	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Fanconi-Bickel syndrome

Benign:3

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. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided

Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 22, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.16

DEOGEN2

Benign

0.25

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.7

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.48

PROVEAN

Benign

3.4

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.023

MPC

0.15

ClinPred

0.018

GERP RS

6.1

Varity_R

0.044

gMVP

0.22

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