chr22-23868562-T-G

Position:

• chr22-23868562-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001024939.4(SLC2A11):​c.211T>G​(p.Ser71Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 3.79

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A11	NM_001024939.4	c.211T>G	p.Ser71Ala	missense_variant	3/12	ENST00000316185.9	NP_001020110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A11	ENST00000316185.9	c.211T>G	p.Ser71Ala	missense_variant	3/12	1	NM_001024939.4	ENSP00000326748.8
ENSG00000251357	ENST00000433835.3	c.97T>G	p.Ser33Ala	missense_variant	2/6	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

May 23, 2024

The c.223T>G (p.S75A) alteration is located in exon 4 (coding exon 3) of the SLC2A11 gene. This alteration results from a T to G substitution at nucleotide position 223, causing the serine (S) at amino acid position 75 to be replaced by an alanine (A). 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	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;.;.;T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.68	T;T;T;T;T;T;.
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D;D;D;D;.;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;D;D;D;.;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D
Polyphen		0.72	P;.;.;.;.;D;.
Vest4		0.43
MutPred		0.83		Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);.;Loss of helix (P = 0.2022);.;.;.;
MVP		0.67
MPC		0.57
ClinPred		0.94	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr22-24210749;