12-7814417-C-T

Variant names:

• chr12-7814417-C-T
• rs1193226420
• NM_001286234.2:c.1393G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286234.2(SLC2A14):​c.1393G>A​(p.Ala465Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC2A14 NM_001286234.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 0 publications found

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]

ACMG classification

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=0.17092425).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A14	NM_001286234.2	MANE Select	c.1393G>A	p.Ala465Thr	missense	Exon 11 of 11	NP_001273163.1	Q8TDB8-2
	SLC2A14	NM_001286237.2		c.1507G>A	p.Ala503Thr	missense	Exon 10 of 10	NP_001273166.1	Q8TDB8-5
	SLC2A14	NM_001286233.2		c.1462G>A	p.Ala488Thr	missense	Exon 16 of 16	NP_001273162.1	Q8TDB8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A14	ENST00000431042.7	TSL:1 MANE Select	c.1393G>A	p.Ala465Thr	missense	Exon 11 of 11	ENSP00000407287.2	Q8TDB8-2
	SLC2A14	ENST00000396589.6	TSL:1	c.1462G>A	p.Ala488Thr	missense	Exon 12 of 12	ENSP00000379834.2	Q8TDB8-1
	SLC2A14	ENST00000543909.5	TSL:1	c.1462G>A	p.Ala488Thr	missense	Exon 16 of 16	ENSP00000440480.1	Q8TDB8-1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151580 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461628 Hom.: 0 Cov.: 71 AF XY: 0.00 AC XY: 0 AN XY: 727126

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111810

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151580 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 73974

African (AFR) AF: 0.00 AC: 0 AN: 41296

American (AMR) AF: 0.00 AC: 0 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Benign	0.63	T
Sift4G	Benign	0.72	T
Polyphen		0.017	B
Vest4		0.14
MutPred		0.43		Gain of catalytic residue at A493 (P = 0.0202)
MVP		0.34
MPC		0.97
ClinPred		0.42	T
GERP RS		3.8
Varity_R		0.10
gMVP		0.12
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs1193226420; hg19: chr12-7967013;