Variant 17-7281958-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001042.3(SLC2A4):c.24A>G(p.Ile8Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000080 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC2A4
NM_001042.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.803

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.124061376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A4	NM_001042.3 linkuse as main transcript	c.24A>G	p.Ile8Met	missense_variant	1/11	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.24A>G	p.Ile8Met	missense_variant	1/11	1	NM_001042.3	ENSP00000320935	P1	P14672-1
SLC2A4	ENST00000572485.5 linkuse as main transcript	c.24A>G	p.Ile8Met	missense_variant, NMD_transcript_variant	1/11	1		ENSP00000461086		P14672-2
SLC2A4	ENST00000571308.5 linkuse as main transcript	c.24A>G	p.Ile8Met	missense_variant	1/10	5		ENSP00000459864
SLC2A4	ENST00000570783.5 linkuse as main transcript	c.24A>G	p.Ile8Met	missense_variant, NMD_transcript_variant	1/10	3		ENSP00000459056

Frequencies

GnomAD3 genomes

AF:

0.00000802

AC:

AN:

124760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1127288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

565794

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000802

AC:

AN:

124760

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

58418

show subpopulations

Gnomad4 AFR

AF:

0.0000308

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.24A>G (p.I8M) alteration is located in exon 1 (coding exon 1) of the SLC2A4 gene. This alteration results from a A to G substitution at nucleotide position 24, causing the isoleucine (I) at amino acid position 8 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

0.91

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.15

N;.

REVEL

Uncertain

0.37

Sift

Benign

0.19

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.0070

B;.

Vest4

0.39

MutPred

0.18

Gain of phosphorylation at S3 (P = 0.0933);Gain of phosphorylation at S3 (P = 0.0933);

MVP

0.64

MPC

0.33

ClinPred

0.091

GERP RS

2.9

Varity_R

0.073

gMVP

0.37

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