Variant chr9-133472079-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017585.4(SLC2A6):c.1466G>A(p.Arg489Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC2A6
NM_017585.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

SLC2A6 (HGNC:11011): (solute carrier family 2 member 6) Hexose transport into mammalian cells is catalyzed by a family of membrane proteins, including SLC2A6, that contain 12 transmembrane domains and a number of critical conserved residues.[supplied by OMIM, Jul 2002]

SLC2A6 links:

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ACMG classification

Classification made for transcript

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
SLC2A6	NM_017585.4 linkuse as main transcript	c.1466G>A	p.Arg489Gln	missense_variant	10/10	ENST00000371899.9
SLC2A6	NM_001145099.2 linkuse as main transcript	c.1280G>A	p.Arg427Gln	missense_variant	9/9
SLC2A6	XM_011518189.4 linkuse as main transcript	c.848G>A	p.Arg283Gln	missense_variant	7/7
SLC2A6	XM_017014237.3 linkuse as main transcript	c.734G>A	p.Arg245Gln	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A6	ENST00000371899.9 linkuse as main transcript	c.1466G>A	p.Arg489Gln	missense_variant	10/10	1	NM_017585.4	P1	Q9UGQ3-1
SLC2A6	ENST00000371897.8 linkuse as main transcript	c.1280G>A	p.Arg427Gln	missense_variant	9/9	2			Q9UGQ3-2
SLC2A6	ENST00000485978.1 linkuse as main transcript	n.2433G>A		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250788

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461218

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.1466G>A (p.R489Q) alteration is located in exon 10 (coding exon 10) of the SLC2A6 gene. This alteration results from a G to A substitution at nucleotide position 1466, causing the arginine (R) at amino acid position 489 to be replaced by a glutamine (Q). 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

Benign

-0.17

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.64

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.50

T;T

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

0.87

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.023

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;D

Vest4

0.13

MutPred

0.86

.;Loss of MoRF binding (P = 0.0938);

MVP

0.64

MPC

0.86

ClinPred

0.85

GERP RS

4.8

Varity_R

0.32

gMVP

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over