chr12-7814428-T-G

Variant names:

• chr12-7814428-T-G
• rs1165268829
• NM_001286234.2:c.1382A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001286234.2(SLC2A14):​c.1382A>C​(p.Asp461Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000082 (0 hom.)
• Consequence: SLC2A14 NM_001286234.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41205388).
• BS2: High AC in GnomAdExome4 at 12 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.1382A>C	p.Asp461Ala	missense	Exon 11 of 11	NP_001273163.1	Q8TDB8-2
	SLC2A14	NM_001286237.2		c.1496A>C	p.Asp499Ala	missense	Exon 10 of 10	NP_001273166.1	Q8TDB8-5
	SLC2A14	NM_001286233.2		c.1451A>C	p.Asp484Ala	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.1382A>C	p.Asp461Ala	missense	Exon 11 of 11	ENSP00000407287.2	Q8TDB8-2
	SLC2A14	ENST00000396589.6	TSL:1	c.1451A>C	p.Asp484Ala	missense	Exon 12 of 12	ENSP00000379834.2	Q8TDB8-1
	SLC2A14	ENST00000543909.5	TSL:1	c.1451A>C	p.Asp484Ala	missense	Exon 16 of 16	ENSP00000440480.1	Q8TDB8-1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151674 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: 0.000193

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

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251162 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461650 Hom.: 0 Cov.: 71 AF XY: 0.00000963 AC XY: 7 AN XY: 727142

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 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: 0.00000180 AC: 2 AN: 1111824

Other (OTH) AF: 0.0000828 AC: 5 AN: 60376

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151792 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74144

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15140

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.00 Hom.: 0

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	0.27
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.24	B
Vest4		0.28
MutPred		0.68		Gain of methylation at R480 (P = 0.083)
MVP		0.48
MPC		2.2
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.48
gMVP		0.46
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1165268829; hg19: chr12-7967024;