9-127397396-T-C

Variant names:

• chr9-127397396-T-C
• rs898398032
• NM_014580.5:c.77T>C

Variant summary

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

The NM_014580.5(SLC2A8):​c.77T>C​(p.Val26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,471,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: SLC2A8 NM_014580.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16470239).

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.77T>C	p.Val26Ala	missense	Exon 2 of 10	NP_055395.2
	SLC2A8	NM_001271711.2		c.77T>C	p.Val26Ala	missense	Exon 2 of 9	NP_001258640.1	Q5VVV9
	SLC2A8	NM_001271712.2		c.-64+110T>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.77T>C	p.Val26Ala	missense	Exon 2 of 10	ENSP00000362469.3	Q9NY64
	SLC2A8	ENST00000373360.7	TSL:1	c.77T>C	p.Val26Ala	missense	Exon 2 of 9	ENSP00000362458.3	Q5VVV9
	SLC2A8	ENST00000954537.1		c.77T>C	p.Val26Ala	missense	Exon 2 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151976 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000416 AC: 3 AN: 72046 AF XY: 0.0000239

Gnomad AFR exome AF: 0.00

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: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000176 AC: 232 AN: 1319690 Hom.: 0 Cov.: 32 AF XY: 0.000171 AC XY: 111 AN XY: 650580

African (AFR) AF: 0.0000757 AC: 2 AN: 26422

American (AMR) AF: 0.0000401 AC: 1 AN: 24918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23208

East Asian (EAS) AF: 0.00 AC: 0 AN: 28234

South Asian (SAS) AF: 0.00 AC: 0 AN: 72582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4386

European-Non Finnish (NFE) AF: 0.000213 AC: 224 AN: 1052350

Other (OTH) AF: 0.0000912 AC: 5 AN: 54818

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151976 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74240

African (AFR) AF: 0.0000725 AC: 3 AN: 41378

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.028
Sift	Uncertain	0.013	D
Sift4G	Benign	0.099	T
Polyphen		0.043	B
Vest4		0.61
MutPred		0.46		Gain of helix (P = 0.0696)
MVP		0.54
MPC		0.26
ClinPred		0.20	T
GERP RS		1.7
PromoterAI		-0.015	Neutral
Varity_R		0.15
gMVP		0.50
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs898398032; hg19: chr9-130159675;