Variant 9-133475074-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.814G>A(p.Val272Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000407 in 1,597,584 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SLC2A6
NM_017585.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11

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:

SLC2A6 (HGNC:):

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=0.08518791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A6	NM_017585.4 linkuse as main transcript	c.814G>A	p.Val272Met	missense_variant	6/10	ENST00000371899.9	NP_060055.2	Q9UGQ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC2A6	ENST00000371899.9 linkuse as main transcript	c.814G>A	p.Val272Met	missense_variant	6/10	1	NM_017585.4	ENSP00000360966.4	Q9UGQ3-1
SLC2A6	ENST00000371897.8 linkuse as main transcript	c.814G>A	p.Val272Met	missense_variant	6/9	2		ENSP00000360964.4	Q9UGQ3-2
SLC2A6	ENST00000485978.1 linkuse as main transcript	n.1402G>A		non_coding_transcript_exon_variant	5/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

224088

Hom.:

AF XY:

0.0000408

AC XY:

AN XY:

122614

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.0000312

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000591

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.0000360

AC:

AN:

1445338

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

717926

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.0000467

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000238

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000334

Gnomad4 OTH exome

AF:

0.0000670

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.23

DANN

Benign

0.88

DEOGEN2

Benign

0.086

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.032

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.21

Sift

Benign

0.26

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.016

B;B

Vest4

0.070

MutPred

0.65

Gain of catalytic residue at V272 (P = 0.0575);Gain of catalytic residue at V272 (P = 0.0575);

MVP

0.26

MPC

0.22

ClinPred

0.015

GERP RS

-8.3

Varity_R

0.016

gMVP

0.30

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