12-7828823-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001286234.2(SLC2A14):​c.557C>T​(p.Pro186Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,102 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SLC2A14
NM_001286234.2 missense

Scores

5
12
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.65
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.923
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC2A14NM_001286234.2 linkc.557C>T p.Pro186Leu missense_variant 6/11 ENST00000431042.7 NP_001273163.1 Q8TDB8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC2A14ENST00000431042.7 linkc.557C>T p.Pro186Leu missense_variant 6/111 NM_001286234.2 ENSP00000407287.2 Q8TDB8-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251460
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461858
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
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
AF:
0.0000131
AC:
2
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsNov 08, 2024The c.626C>T (p.P209L) alteration is located in exon 7 (coding exon 5) of the SLC2A14 gene. This alteration results from a C to T substitution at nucleotide position 626, causing the proline (P) at amino acid position 209 to be replaced by a leucine (L). 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
0.70
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.42
.;.;T;T;.;T;.;.
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.85
.;D;D;.;D;.;.;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.26
D
MutationAssessor
Uncertain
2.4
.;.;M;M;.;M;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-8.7
D;D;.;D;D;D;D;D
REVEL
Pathogenic
0.70
Sift
Uncertain
0.0020
D;D;.;D;D;D;D;D
Sift4G
Uncertain
0.037
D;T;D;D;D;D;T;D
Polyphen
0.92
P;.;P;P;P;P;.;.
Vest4
0.89
MutPred
0.68
.;.;Gain of catalytic residue at W208 (P = 0);Gain of catalytic residue at W208 (P = 0);.;Gain of catalytic residue at W208 (P = 0);.;.;
MVP
0.43
MPC
0.68
ClinPred
0.96
D
GERP RS
3.9
Varity_R
0.74
gMVP
0.58

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.

Other links and lift over

dbSNP: rs202006975; hg19: chr12-7981419; COSMIC: COSV61585665; COSMIC: COSV61585665; API