Genetic Variant SLC2A8:p.Ile51Met (chr9-127397472-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014580.5(SLC2A8):c.153C>G(p.Ile51Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,481,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

SLC2A8
NM_014580.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.180

Publications

0 publications found

Variant links:

Genes affected

SLC2A8 (HGNC:13812): (solute carrier family 2 member 8) This gene belongs to the solute carrier 2A family, which includes intracellular glucose transporters. Based on sequence comparison, the glucose transporters are grouped into three classes and this gene is a member of class II. The encoded protein, like other members of the family, contains several conserved residues and motifs and 12 transmembrane domains with both amino and carboxyl ends being on the cytosolic side of the membrane. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

SLC2A8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21317363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014580.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A8	NM_014580.5	MANE Select	c.153C>G	p.Ile51Met	missense	Exon 2 of 10	NP_055395.2
SLC2A8	NM_001271711.2		c.153C>G	p.Ile51Met	missense	Exon 2 of 9	NP_001258640.1	Q5VVV9
SLC2A8	NM_001271712.2		c.-64+186C>G		intron	N/A	NP_001258641.1	A0A087WT42

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A8	ENST00000373371.8	TSL:1 MANE Select	c.153C>G	p.Ile51Met	missense	Exon 2 of 10	ENSP00000362469.3	Q9NY64
SLC2A8	ENST00000373360.7	TSL:1	c.153C>G	p.Ile51Met	missense	Exon 2 of 9	ENSP00000362458.3	Q5VVV9
SLC2A8	ENST00000954537.1		c.153C>G	p.Ile51Met	missense	Exon 2 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.0000125

AC:

AN:

80086

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000451

AC:

AN:

1329124

Hom.:

Cov.:

AF XY:

0.00000305

AC XY:

AN XY:

655254

show subpopulations

African (AFR)

AF:

0.000187

AC:

AN:

26708

American (AMR)

AF:

0.00

AC:

AN:

27364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23382

East Asian (EAS)

AF:

0.00

AC:

AN:

29112

South Asian (SAS)

AF:

0.00

AC:

AN:

73498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4428

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1056378

Other (OTH)

AF:

0.0000181

AC:

AN:

55272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41458

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000945

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.21

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.077

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.5

PhyloP100

0.18

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.5

REVEL

Benign

0.28

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.49

MutPred

0.57

Gain of disorder (P = 0.0506)

MVP

0.59

MPC

0.77

ClinPred

0.35

GERP RS

3.5

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.67

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over