chr9-127397431-C-G

Variant names:

• chr9-127397431-C-G
• rs765179278
• NM_014580.5:c.112C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014580.5(SLC2A8):​c.112C>G​(p.Leu38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,334,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: SLC2A8 NM_014580.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.381
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33452743).

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.112C>G	p.Leu38Val	missense	Exon 2 of 10	NP_055395.2
	SLC2A8	NM_001271711.2		c.112C>G	p.Leu38Val	missense	Exon 2 of 9	NP_001258640.1	Q5VVV9
	SLC2A8	NM_001271712.2		c.-64+145C>G		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.112C>G	p.Leu38Val	missense	Exon 2 of 10	ENSP00000362469.3	Q9NY64
	SLC2A8	ENST00000373360.7	TSL:1	c.112C>G	p.Leu38Val	missense	Exon 2 of 9	ENSP00000362458.3	Q5VVV9
	SLC2A8	ENST00000954537.1		c.112C>G	p.Leu38Val	missense	Exon 2 of 10	ENSP00000624596.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000121 AC: 1 AN: 82844 AF XY: 0.0000212

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: 0.0000335

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1334904 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 658176

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26936

American (AMR) AF: 0.00 AC: 0 AN: 28724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23632

East Asian (EAS) AF: 0.00 AC: 0 AN: 29216

South Asian (SAS) AF: 0.00 AC: 0 AN: 74174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4574

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1059006

Other (OTH) AF: 0.00 AC: 0 AN: 55586

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

Alfa AF: 0.000141 Hom.: 0

ExAC AF: 0.0000534 AC: 1

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	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.38
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.27
Sift	Uncertain	0.025	D
Sift4G	Benign	0.22	T
Polyphen		0.94	P
Vest4		0.43
MutPred		0.60		Gain of sheet (P = 0.0477)
MVP		0.67
MPC		0.24
ClinPred		0.87	D
GERP RS		4.4
PromoterAI		0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.55
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs765179278; hg19: chr9-130159710;