22-23857517-C-T

Variant names:

• chr22-23857517-C-T
• rs16986337
• ENST00000398356.6:c.28C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398356.6(SLC2A11):​c.28C>T​(p.Arg10Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 1,612,776 control chromosomes in the GnomAD database, including 3,608 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (1629 hom., cov: 31)
  • Exomes 𝑓: 0.029 (1979 hom.)
• Consequence: SLC2A11 ENST00000398356.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 14 publications found

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]

ENSG00000272973 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005146295).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398356.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A11	NM_001282864.2		c.28C>T	p.Arg10Trp	missense	Exon 1 of 11	NP_001269793.1
	SLC2A11	NM_030807.5		c.28C>T	p.Arg10Trp	missense	Exon 2 of 13	NP_110434.3
	SLC2A11	NR_104248.2		n.155C>T		non_coding_transcript_exon	Exon 2 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A11	ENST00000398356.6	TSL:1	c.28C>T	p.Arg10Trp	missense	Exon 2 of 13	ENSP00000381399.2
	SLC2A11	ENST00000467660.5	TSL:1	n.143C>T		non_coding_transcript_exon	Exon 2 of 9
	SLC2A11	ENST00000345044.10	TSL:1	c.21+526C>T		intron	N/A	ENSP00000342542.5

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14366 AN: 151364 Hom.: 1623 Cov.: 31

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.00908

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0960

GnomAD2 exomes AF: 0.0415 AC: 10287 AN: 248108 AF XY: 0.0362

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.0363

Gnomad ASJ exome AF: 0.0662

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.0289

Gnomad OTH exome AF: 0.0470

GnomAD4 exome AF: 0.0293 AC: 42847 AN: 1461300 Hom.: 1979 Cov.: 33 AF XY: 0.0281 AC XY: 20458 AN XY: 726970

African (AFR) AF: 0.288 AC: 9620 AN: 33460

American (AMR) AF: 0.0390 AC: 1742 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 1683 AN: 26102

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39686

South Asian (SAS) AF: 0.00738 AC: 636 AN: 86194

European-Finnish (FIN) AF: 0.0139 AC: 742 AN: 53292

Middle Eastern (MID) AF: 0.0780 AC: 445 AN: 5706

European-Non Finnish (NFE) AF: 0.0228 AC: 25312 AN: 1111816

Other (OTH) AF: 0.0441 AC: 2664 AN: 60352

GnomAD4 genome AF: 0.0951 AC: 14403 AN: 151476 Hom.: 1629 Cov.: 31 AF XY: 0.0910 AC XY: 6741 AN XY: 74040

African (AFR) AF: 0.270 AC: 11048 AN: 40934

American (AMR) AF: 0.0582 AC: 889 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4816

European-Finnish (FIN) AF: 0.00908 AC: 96 AN: 10578

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0273 AC: 1857 AN: 67958

Other (OTH) AF: 0.0950 AC: 200 AN: 2106

Alfa AF: 0.0532 Hom.: 1765

Bravo AF: 0.108

TwinsUK AF: 0.0181 AC: 67

ALSPAC AF: 0.0226 AC: 87

ESP6500AA AF: 0.273 AC: 1204

ESP6500EA AF: 0.0310 AC: 267

ExAC AF: 0.0466 AC: 5657

Asia WGS AF: 0.0200 AC: 70 AN: 3478

EpiCase AF: 0.0302

EpiControl AF: 0.0297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	6.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.11
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.016	D
Vest4		0.19
MPC		0.34
ClinPred		0.059	T
GERP RS		0.75
PromoterAI		-0.066	Neutral
gMVP		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16986337; hg19: chr22-24199704;