22-23882536-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024939.4(SLC2A11):c.772G>A(p.Gly258Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,454,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SLC2A11 NM_001024939.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

Genes affected

SLC2A11 (HGNC:14239): (solute carrier family 2 member 11) This gene belongs to a family of proteins that mediate the transport of sugars across the cell membrane. The encoded protein transports glucose and fructose. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0750497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A11	NM_001024939.4	c.772G>A	p.Gly258Ser	missense_variant	7/12	ENST00000316185.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A11	ENST00000316185.9	c.772G>A	p.Gly258Ser	missense_variant	7/12	1	NM_001024939.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000603 AC: 14 AN: 232258 Hom.: 0 AF XY: 0.0000628 AC XY: 8 AN XY: 127420

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 SAS exome AF: 0.000476

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000165 AC: 24 AN: 1454342 Hom.: 0 Cov.: 33 AF XY: 0.0000194 AC XY: 14 AN XY: 723184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000246

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000331 AC: 4

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.784G>A (p.G262S) alteration is located in exon 8 (coding exon 7) of the SLC2A11 gene. This alteration results from a G to A substitution at nucleotide position 784, causing the glycine (G) at amino acid position 262 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	19
Dann	Benign	0.86
DEOGEN2	Benign	0.068	T;.;T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.71	N;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.1	N;N;.;N
REVEL	Benign	0.085
Sift	Benign	0.46	T;T;.;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.0070	B;.;.;B
Vest4		0.17
MutPred		0.33		Gain of phosphorylation at G255 (P = 0.0503);.;.;.;
MVP		0.28
MPC		0.57
ClinPred		0.065	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.077
gMVP		0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs572438357; hg19: chr22-24224723;