Variant chr9-133473986-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017585.4(SLC2A6):c.1030G>A(p.Val344Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000654 in 1,605,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SLC2A6
NM_017585.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.203

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0072552264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A6	NM_017585.4 linkuse as main transcript	c.1030G>A	p.Val344Ile	missense_variant	7/10	ENST00000371899.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A6	ENST00000371899.9 linkuse as main transcript	c.1030G>A	p.Val344Ile	missense_variant	7/10	1	NM_017585.4	P1	Q9UGQ3-1
SLC2A6	ENST00000371897.8 linkuse as main transcript	c.1030G>A	p.Val344Ile	missense_variant	7/9	2			Q9UGQ3-2
SLC2A6	ENST00000485978.1 linkuse as main transcript	n.1618G>A		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

241078

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

131296

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.0000673

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000385

AC:

AN:

1452900

Hom.:

Cov.:

AF XY:

0.0000388

AC XY:

AN XY:

721704

show subpopulations

Gnomad4 AFR exome

AF:

0.000689

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000322

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000890

Hom.:

Bravo

AF:

0.000416

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 22, 2021

The c.1030G>A (p.V344I) alteration is located in exon 7 (coding exon 7) of the SLC2A6 gene. This alteration results from a G to A substitution at nucleotide position 1030, causing the valine (V) at amino acid position 344 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

0.083

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.0

DANN

Benign

0.85

DEOGEN2

Benign

0.057

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.25

M_CAP

Benign

0.080

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.67

N;N

MutationTaster

Benign

0.92

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.040

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.12

B;B

Vest4

0.077

MVP

0.24

MPC

0.17

ClinPred

0.0031

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.32

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