Genetic Variant NM_001286234.2:c.1441G>T (chr12-7814369-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286234.2(SLC2A14):c.1441G>T(p.Val481Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V481I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 26)

Failed GnomAD Quality Control

Consequence

SLC2A14
NM_001286234.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

Publications

2 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08967531).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286234.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A14	NM_001286234.2	MANE Select	c.1441G>T	p.Val481Phe	missense	Exon 11 of 11	NP_001273163.1	Q8TDB8-2
SLC2A14	NM_001286237.2		c.1555G>T	p.Val519Phe	missense	Exon 10 of 10	NP_001273166.1	Q8TDB8-5
SLC2A14	NM_001286233.2		c.1510G>T	p.Val504Phe	missense	Exon 16 of 16	NP_001273162.1	Q8TDB8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A14	ENST00000431042.7	TSL:1 MANE Select	c.1441G>T	p.Val481Phe	missense	Exon 11 of 11	ENSP00000407287.2	Q8TDB8-2
SLC2A14	ENST00000396589.6	TSL:1	c.1510G>T	p.Val504Phe	missense	Exon 12 of 12	ENSP00000379834.2	Q8TDB8-1
SLC2A14	ENST00000543909.5	TSL:1	c.1510G>T	p.Val504Phe	missense	Exon 16 of 16	ENSP00000440480.1	Q8TDB8-1

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000692

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

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000669

AC:

AN:

149486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72718

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41118

American (AMR)

AF:

0.0000692

AC:

AN:

14448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67274

Other (OTH)

AF:

0.00

AC:

AN:

2026

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.14

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0098

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.71

M_CAP

Benign

0.020

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.0

PhyloP100

0.049

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.50

REVEL

Benign

0.18

Sift

Uncertain

0.019

Sift4G

Uncertain

0.054

Polyphen

0.86

Vest4

0.11

MutPred

0.28

Gain of catalytic residue at N508 (P = 0.0483)

MVP

0.19

MPC

1.3

ClinPred

0.12

GERP RS

-2.5

Varity_R

0.081

gMVP

0.44

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over