chr22-23875151-G-A

Position:

• chr22-23875151-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001024939.4(SLC2A11):​c.325G>A​(p.Val109Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SLC2A11 NM_001024939.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.505

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]

ENSG00000251357 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31766266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A11	NM_001024939.4	c.325G>A	p.Val109Met	missense_variant	4/12	ENST00000316185.9	NP_001020110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A11	ENST00000316185.9	c.325G>A	p.Val109Met	missense_variant	4/12	1	NM_001024939.4	ENSP00000326748.8
ENSG00000251357	ENST00000433835.3	c.211G>A	p.Val71Met	missense_variant	3/6	5		ENSP00000400325.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 04, 2023

The c.337G>A (p.V113M) alteration is located in exon 5 (coding exon 4) of the SLC2A11 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the valine (V) at amino acid position 113 to be replaced by a methionine (M). 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	0.15
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;.;.;T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.89	D;D;D;D;D;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;.;.;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.2	N;N;N;.;N;N
REVEL	Benign	0.18
Sift	Benign	0.077	T;T;T;.;T;D
Sift4G	Benign	0.14	T;T;D;T;T;D
Polyphen		0.13	B;.;.;.;B;.
Vest4		0.15
MutPred		0.63		Loss of catalytic residue at V106 (P = 0.0056);.;Loss of catalytic residue at V106 (P = 0.0056);.;.;.;
MVP		0.45
MPC		0.61
ClinPred		0.34	T
GERP RS		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24217338;