Variant 6-134028413-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_145176.3(SLC2A12):c.1412A>G(p.Tyr471Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

SLC2A12
NM_145176.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

Variant links:

Genes affected

SLC2A12 (HGNC:18067): (solute carrier family 2 member 12) SLC2A12 belongs to a family of transporters that catalyze the uptake of sugars through facilitated diffusion (Rogers et al., 2002). This family of transporters show conservation of 12 transmembrane helices as well as functionally significant amino acid residues (Joost and Thorens, 2001 [PubMed 11780753]).[supplied by OMIM, Mar 2008]

SLC2A12 links:

Genome browser will be placed here

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	Protein	UniProt
SLC2A12	NM_145176.3 linkuse as main transcript	c.1412A>G	p.Tyr471Cys	missense_variant	2/5	ENST00000275230.6	NP_660159.1	Q8TD20
SLC2A12	XM_006715349.5 linkuse as main transcript	c.1412A>G	p.Tyr471Cys	missense_variant	2/3		XP_006715412.1
SLC2A12	XM_017010311.3 linkuse as main transcript	c.1412A>G	p.Tyr471Cys	missense_variant	2/3		XP_016865800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A12	ENST00000275230.6 linkuse as main transcript	c.1412A>G	p.Tyr471Cys	missense_variant	2/5	1	NM_145176.3	ENSP00000275230.5		Q8TD20

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000998

AC:

AN:

250496

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.000300

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461220

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.000269

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:

0.0000828

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000844

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000906

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 23, 2023

The c.1412A>G (p.Y471C) alteration is located in exon 2 (coding exon 2) of the SLC2A12 gene. This alteration results from a A to G substitution at nucleotide position 1412, causing the tyrosine (Y) at amino acid position 471 to be replaced by a cysteine (C). 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

0.28

BayesDel_addAF

Benign

-0.0079

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Benign

0.057

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.63

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.082

Vest4

0.90

MVP

0.75

MPC

0.77

ClinPred

0.36

GERP RS

4.1

Varity_R

0.63

gMVP

0.85

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