Variant chr17-7283546-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042.3(SLC2A4):c.224G>A(p.Gly75Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

SLC2A4
NM_001042.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00900

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14619663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A4	NM_001042.3 linkuse as main transcript	c.224G>A	p.Gly75Asp	missense_variant	3/11	ENST00000317370.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A4	ENST00000317370.13 linkuse as main transcript	c.224G>A	p.Gly75Asp	missense_variant	3/11	1	NM_001042.3	P1	P14672-1
	ENST00000576271.1 linkuse as main transcript	n.46-230C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

Feb 27, 2023

The c.224G>A (p.G75D) alteration is located in exon 3 (coding exon 3) of the SLC2A4 gene. This alteration results from a G to A substitution at nucleotide position 224, causing the glycine (G) at amino acid position 75 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.66

MutationTaster

Benign

0.83

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

N;.;N

REVEL

Uncertain

0.37

Sift

Benign

0.18

T;.;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.43

MutPred

0.32

Loss of catalytic residue at G75 (P = 0.1204);Loss of catalytic residue at G75 (P = 0.1204);.;

MVP

0.62

MPC

0.33

ClinPred

0.073

GERP RS

3.1

Varity_R

0.15

gMVP

0.79

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