chr9-127397936-G-C

Variant names:

• chr9-127397936-G-C
• rs745733061
• NM_014580.5:c.251G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014580.5(SLC2A8):​c.251G>C​(p.Gly84Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000392 in 1,531,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G84V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SLC2A8 NM_014580.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.51
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A8	NM_014580.5	MANE Select	c.251G>C	p.Gly84Ala	missense	Exon 3 of 10	NP_055395.2
	SLC2A8	NM_001271711.2		c.251G>C	p.Gly84Ala	missense	Exon 3 of 9	NP_001258640.1	Q5VVV9
	SLC2A8	NM_001271712.2		c.-64+650G>C		intron	N/A	NP_001258641.1	A0A087WT42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A8	ENST00000373371.8	TSL:1 MANE Select	c.251G>C	p.Gly84Ala	missense	Exon 3 of 10	ENSP00000362469.3	Q9NY64
	SLC2A8	ENST00000373360.7	TSL:1	c.251G>C	p.Gly84Ala	missense	Exon 3 of 9	ENSP00000362458.3	Q5VVV9
	SLC2A8	ENST00000954537.1		c.251G>C	p.Gly84Ala	missense	Exon 3 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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 AF: 0.00000290 AC: 4 AN: 1379600 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 680774

African (AFR) AF: 0.00 AC: 0 AN: 31258

American (AMR) AF: 0.0000281 AC: 1 AN: 35590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25028

East Asian (EAS) AF: 0.00 AC: 0 AN: 35462

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 79046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4346

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077514

Other (OTH) AF: 0.00 AC: 0 AN: 57574

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	-0.11	N
PhyloP100		9.5
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.58
Sift	Benign	0.070	T
Sift4G	Benign	0.48	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.71		Gain of MoRF binding (P = 0.1619)
MVP		0.82
MPC		0.78
ClinPred		0.99	D
GERP RS		5.3
PromoterAI		0.0022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.44
gMVP		0.72
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs745733061; hg19: chr9-130160215;