chr12-7814498-C-T

Variant names:

• chr12-7814498-C-T
• rs757902444
• NM_001286234.2:c.1312G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001286234.2(SLC2A14):​c.1312G>A​(p.Gly438Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SLC2A14 NM_001286234.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.814
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 26 AD gene.

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.1312G>A	p.Gly438Ser	missense	Exon 11 of 11	NP_001273163.1	Q8TDB8-2
	SLC2A14	NM_001286237.2		c.1426G>A	p.Gly476Ser	missense	Exon 10 of 10	NP_001273166.1	Q8TDB8-5
	SLC2A14	NM_001286233.2		c.1381G>A	p.Gly461Ser	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.1312G>A	p.Gly438Ser	missense	Exon 11 of 11	ENSP00000407287.2	Q8TDB8-2
	SLC2A14	ENST00000396589.6	TSL:1	c.1381G>A	p.Gly461Ser	missense	Exon 12 of 12	ENSP00000379834.2	Q8TDB8-1
	SLC2A14	ENST00000543909.5	TSL:1	c.1381G>A	p.Gly461Ser	missense	Exon 16 of 16	ENSP00000440480.1	Q8TDB8-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151630 Hom.: 0 Cov.: 31

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251052 AF XY: 0.0000221

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461634 Hom.: 0 Cov.: 37 AF XY: 0.0000165 AC XY: 12 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44704

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111832

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151630 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73988

African (AFR) AF: 0.00 AC: 0 AN: 41220

American (AMR) AF: 0.00 AC: 0 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10506

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.68
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.85	L
PhyloP100		0.81
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.16
Sift	Uncertain	0.015	D
Sift4G	Benign	0.074	T
Polyphen		0.21	B
Vest4		0.074
MutPred		0.62		Gain of catalytic residue at I464 (P = 0.0021)
MVP		0.22
MPC		1.0
ClinPred		0.063	T
GERP RS		2.7
Varity_R		0.048
gMVP		0.39
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757902444; hg19: chr12-7967094;