Genetic Variant NM_001042.3:c.236C>G (chr17-7283558-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001042.3(SLC2A4):c.236C>G(p.Thr79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,614,106 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 18 hom. )

Consequence

SLC2A4
NM_001042.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56

Publications

11 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:

ENSG00000263342 (HGNC:):

ENSG00000263342 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007543564).

BP6

Variant 17-7283558-C-G is Benign according to our data. Variant chr17-7283558-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647323.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A4	NM_001042.3 link	c.236C>G	p.Thr79Ser	missense_variant	Exon 3 of 11	ENST00000317370.13	NP_001033.1	P14672-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A4	ENST00000317370.13 link	c.236C>G	p.Thr79Ser	missense_variant	Exon 3 of 11	1	NM_001042.3	ENSP00000320935.8		P14672-1

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

485

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00450

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00350

AC:

881

AN:

251394

AF XY:

0.00354

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00713

Gnomad NFE exome

AF:

0.00456

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00436

AC:

6380

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

3179

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.00203

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00551

AC:

144

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00150

AC:

129

AN:

86258

European-Finnish (FIN)

AF:

0.00706

AC:

377

AN:

53388

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00480

AC:

5333

AN:

1112000

Other (OTH)

AF:

0.00452

AC:

273

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

420

840

1260

1680

2100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00319

AC:

485

AN:

152256

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

234

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41556

American (AMR)

AF:

0.00209

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00622

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00450

AC:

306

AN:

68010

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.00303

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00318

AC:

386

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00522

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC2A4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.077

T;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.0075

T;T;T

MetaSVM

Benign

-0.82

PhyloP100

1.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.42

N;.;N

REVEL

Benign

0.10

Sift

Benign

0.64

T;.;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.0090

B;.;B

Vest4

0.14

MutPred

0.41

Gain of disorder (P = 0.0679);Gain of disorder (P = 0.0679);.;

MVP

0.64

MPC

0.23

ClinPred

0.0035

GERP RS

4.2

Varity_R

0.16

gMVP

0.26

Mutation Taster

=100/0

polymorphism

(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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NM_001042.3:c.236C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over