22-23877740-C-G

Position:

• chr22-23877740-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001024939.4(SLC2A11):​c.565C>G​(p.Gln189Glu) 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. 15/21 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: 0.0340

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04173076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A11	NM_001024939.4	c.565C>G	p.Gln189Glu	missense_variant	6/12	ENST00000316185.9	NP_001020110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A11	ENST00000316185.9	c.565C>G	p.Gln189Glu	missense_variant	6/12	1	NM_001024939.4	ENSP00000326748.8
ENSG00000251357	ENST00000433835.3	c.431+569C>G		intron_variant		5		ENSP00000400325.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 02, 2024

The c.577C>G (p.Q193E) alteration is located in exon 7 (coding exon 6) of the SLC2A11 gene. This alteration results from a C to G substitution at nucleotide position 577, causing the glutamine (Q) at amino acid position 193 to be replaced by a glutamic acid (E). 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	0.060
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.4
DANN	Benign	0.74
DEOGEN2	Benign	0.037	T;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.042	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.13	N;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	1.0	N;N;.;N
REVEL	Benign	0.076
Sift	Benign	1.0	T;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;.;.;B
Vest4		0.092
MutPred		0.48		Gain of stability (P = 0.0311);.;.;.;
MVP		0.26
MPC		0.22
ClinPred		0.023	T
GERP RS		1.4
Varity_R		0.076
gMVP		0.065

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24219927;