Genetic Variant NM_014580.5:c.245C>G (chr9-127397930-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014580.5(SLC2A8):c.245C>G(p.Ala82Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,530,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A82V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SLC2A8
NM_014580.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.245C>G	p.Ala82Gly	missense	Exon 3 of 10	NP_055395.2
SLC2A8	NM_001271711.2		c.245C>G	p.Ala82Gly	missense	Exon 3 of 9	NP_001258640.1	Q5VVV9
SLC2A8	NM_001271712.2		c.-64+644C>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.245C>G	p.Ala82Gly	missense	Exon 3 of 10	ENSP00000362469.3	Q9NY64
SLC2A8	ENST00000373360.7	TSL:1	c.245C>G	p.Ala82Gly	missense	Exon 3 of 9	ENSP00000362458.3	Q5VVV9
SLC2A8	ENST00000954537.1		c.245C>G	p.Ala82Gly	missense	Exon 3 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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

GnomAD2 exomes

AF:

0.0000158

AC:

AN:

126446

AF XY:

0.0000145

show subpopulations

Gnomad AFR exome

AF:

0.000333

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:

0.00000145

AC:

AN:

1378110

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

679968

show subpopulations

African (AFR)

AF:

0.0000642

AC:

AN:

31156

American (AMR)

AF:

0.00

AC:

AN:

35476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24954

East Asian (EAS)

AF:

0.00

AC:

AN:

35346

South Asian (SAS)

AF:

0.00

AC:

AN:

78856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4264

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076848

Other (OTH)

AF:

0.00

AC:

AN:

57518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.97

PhyloP100

0.35

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.30

Sift

Benign

0.10

Sift4G

Uncertain

0.059

Polyphen

0.010

Vest4

0.36

MutPred

0.73

Loss of stability (P = 0.1694)

MVP

0.77

MPC

0.21

ClinPred

0.064

GERP RS

3.1

PromoterAI

0.076

Neutral

(source)

Varity_R

0.18

gMVP

0.48

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.34

Position offset: -25

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

Publications

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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