Variant chr9-133473134-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017585.4(SLC2A6):c.1339G>A(p.Val447Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,611,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SLC2A6
NM_017585.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.559

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06835985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC2A6	NM_017585.4 linkuse as main transcript	c.1339G>A	p.Val447Ile	missense_variant	9/10	ENST00000371899.9
SLC2A6	NM_001145099.2 linkuse as main transcript	c.1153G>A	p.Val385Ile	missense_variant	8/9
SLC2A6	XM_011518189.4 linkuse as main transcript	c.721G>A	p.Val241Ile	missense_variant	6/7
SLC2A6	XM_017014237.3 linkuse as main transcript	c.607G>A	p.Val203Ile	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A6	ENST00000371899.9 linkuse as main transcript	c.1339G>A	p.Val447Ile	missense_variant	9/10	1	NM_017585.4	P1	Q9UGQ3-1
SLC2A6	ENST00000371897.8 linkuse as main transcript	c.1153G>A	p.Val385Ile	missense_variant	8/9	2			Q9UGQ3-2
SLC2A6	ENST00000485978.1 linkuse as main transcript	n.2306G>A		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000487

AC:

AN:

246318

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

134010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1459172

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725908

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000413

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Dec 28, 2022

The c.1339G>A (p.V447I) 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 1339, causing the valine (V) at amino acid position 447 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.24

M_CAP

Benign

0.048

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.075

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.11

Sift

Benign

0.45

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.31

B;B

Vest4

0.12

MutPred

0.41

.;Gain of ubiquitination at K450 (P = 0.0954);

MVP

0.21

MPC

0.17

ClinPred

0.052

GERP RS

4.8

Varity_R

0.033

gMVP

0.18

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