Variant 12-7828712-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001286234.2(SLC2A14):c.668C>A(p.Ala223Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC2A14
NM_001286234.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.19

Variant links:

Genes affected

SLC2A14 (HGNC:18301): (solute carrier family 2 member 14) Members of the glucose transporter (GLUT) family, including SLC2A14, are highly conserved integral membrane proteins that transport hexoses such as glucose and fructose into all mammalian cells. GLUTs show tissue and cell-type specific expression (Wu and Freeze, 2002 [PubMed 12504846]).[supplied by OMIM, Mar 2008]

SLC2A14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A14	NM_001286234.2 linkuse as main transcript	c.668C>A	p.Ala223Asp	missense_variant	6/11	ENST00000431042.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A14	ENST00000431042.7 linkuse as main transcript	c.668C>A	p.Ala223Asp	missense_variant	6/11	1	NM_001286234.2	P1	Q8TDB8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251364

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727164

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 03, 2022

The c.737C>A (p.A246D) alteration is located in exon 7 (coding exon 5) of the SLC2A14 gene. This alteration results from a C to A substitution at nucleotide position 737, causing the alanine (A) at amino acid position 246 to be replaced by an aspartic acid (D). 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

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.17

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.93

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.7

D;D;.;D;D;D;D;D

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

D;D;.;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;D;D;.;.

Vest4

0.62

MutPred

0.75

.;.;Loss of MoRF binding (P = 0.0283);Loss of MoRF binding (P = 0.0283);.;Loss of MoRF binding (P = 0.0283);.;.;

MVP

0.72

MPC

1.0

ClinPred

0.99

GERP RS

3.9

Varity_R

0.87

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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