Variant 9-133473107-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017585.4(SLC2A6):c.1366G>A(p.Val456Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC2A6
NM_017585.4 missense, splice_region

Scores

Splicing: ADA: 0.00006821

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29940602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC2A6	NM_017585.4 linkuse as main transcript	c.1366G>A	p.Val456Met	missense_variant, splice_region_variant	9/10	ENST00000371899.9
SLC2A6	NM_001145099.2 linkuse as main transcript	c.1180G>A	p.Val394Met	missense_variant, splice_region_variant	8/9
SLC2A6	XM_011518189.4 linkuse as main transcript	c.748G>A	p.Val250Met	missense_variant, splice_region_variant	6/7
SLC2A6	XM_017014237.3 linkuse as main transcript	c.634G>A	p.Val212Met	missense_variant, splice_region_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A6	ENST00000371899.9 linkuse as main transcript	c.1366G>A	p.Val456Met	missense_variant, splice_region_variant	9/10	1	NM_017585.4	P1	Q9UGQ3-1
SLC2A6	ENST00000371897.8 linkuse as main transcript	c.1180G>A	p.Val394Met	missense_variant, splice_region_variant	8/9	2			Q9UGQ3-2
SLC2A6	ENST00000485978.1 linkuse as main transcript	n.2333G>A		splice_region_variant, non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 08, 2022

The c.1366G>A (p.V456M) alteration is located in exon 9 (coding exon 9) of the SLC2A6 gene. This alteration results from a G to A substitution at nucleotide position 1366, causing the valine (V) at amino acid position 456 to be replaced by a methionine (M). 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

0.26

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.078

.;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.74

M_CAP

Benign

0.040

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.3

.;L

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;T

Sift4G

Benign

0.56

T;T

Polyphen

1.0

D;D

Vest4

0.25

MutPred

0.66

.;Loss of glycosylation at S457 (P = 0.1237);

MVP

0.56

MPC

0.78

ClinPred

0.82

GERP RS

3.9

Varity_R

0.080

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000068

dbscSNV1_RF

Benign

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over