22-23882465-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001024939.4(SLC2A11):c.701G>A(p.Arg234Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,388,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SLC2A11 NM_001024939.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.353

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
• BP6: Variant 22-23882465-G-A is Benign according to our data. Variant chr22-23882465-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3164099.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A11	NM_001024939.4	c.701G>A	p.Arg234Gln	missense_variant	7/12	ENST00000316185.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A11	ENST00000316185.9	c.701G>A	p.Arg234Gln	missense_variant	7/12	1	NM_001024939.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000703 AC: 1 AN: 142342 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 77076

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: 0.0000456

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1388306 Hom.: 0 Cov.: 31 AF XY: 0.00000292 AC XY: 2 AN XY: 684744

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000388 AC: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.95
Dann	Benign	0.76
DEOGEN2	Benign	0.044	T;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0084	N
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.99	N;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.54	N;N;.;N
REVEL	Benign	0.070
Sift	Benign	1.0	T;T;.;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.013	B;.;.;B
Vest4		0.048
MutPred		0.43		Loss of methylation at R231 (P = 0.0203);.;.;.;
MVP		0.32
MPC		0.22
ClinPred		0.018	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.014
gMVP		0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs766659555; hg19: chr22-24224652; COSMIC: COSV55391825; COSMIC: COSV55391825;