22-23862198-C-T

Position:

• chr22-23862198-C-T

Variant summary

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

The NM_001024939.4(SLC2A11):​c.125C>T​(p.Thr42Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC2A11 NM_001024939.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A11	NM_001024939.4	c.125C>T	p.Thr42Ile	missense_variant	2/12	ENST00000316185.9	NP_001020110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A11	ENST00000316185.9	c.125C>T	p.Thr42Ile	missense_variant	2/12	1	NM_001024939.4	ENSP00000326748.8
ENSG00000251357	ENST00000433835.3	c.11C>T	p.Thr4Ile	missense_variant	1/6	5		ENSP00000400325.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461742 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727186

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Nov 07, 2024

The c.137C>T (p.T46I) alteration is located in exon 3 (coding exon 2) of the SLC2A11 gene. This alteration results from a C to T substitution at nucleotide position 137, causing the threonine (T) at amino acid position 46 to be replaced by an isoleucine (I). 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	Uncertain	0.40
BayesDel_addAF	Benign	0.0016	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;.;.;T;.;.
Eigen	Benign	0.028
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.83	T;D;T;D;T;T;.
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.8	D;D;D;D;.;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;D;D;.;D;D
Sift4G	Uncertain	0.025	D;D;D;T;D;D;D
Polyphen		0.93	P;.;.;.;.;D;.
Vest4		0.47
MutPred		0.50		Loss of glycosylation at T39 (P = 0.0596);Loss of glycosylation at T39 (P = 0.0596);.;Loss of glycosylation at T39 (P = 0.0596);.;.;.;
MVP		0.55
MPC		0.29
ClinPred		0.98	D
GERP RS		1.3
Varity_R		0.33
gMVP		0.66

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: chr22-24204385;