chr12-7827673-C-T

Variant names:

• chr12-7827673-C-T
• rs778525180
• NM_001286234.2:c.686G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001286234.2(SLC2A14):​c.686G>A​(p.Arg229Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 143,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC2A14 NM_001286234.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.265
• Publications: 7 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03693798).
• BS2: High AC in GnomAd4 at 5 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.686G>A	p.Arg229Gln	missense	Exon 7 of 11	NP_001273163.1	Q8TDB8-2
	SLC2A14	NM_001286237.2		c.800G>A	p.Arg267Gln	missense	Exon 6 of 10	NP_001273166.1	Q8TDB8-5
	SLC2A14	NM_001286233.2		c.755G>A	p.Arg252Gln	missense	Exon 12 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.686G>A	p.Arg229Gln	missense	Exon 7 of 11	ENSP00000407287.2	Q8TDB8-2
	SLC2A14	ENST00000396589.6	TSL:1	c.755G>A	p.Arg252Gln	missense	Exon 8 of 12	ENSP00000379834.2	Q8TDB8-1
	SLC2A14	ENST00000543909.5	TSL:1	c.755G>A	p.Arg252Gln	missense	Exon 12 of 16	ENSP00000440480.1	Q8TDB8-1

Frequencies

GnomAD3 genomes AF: 0.0000348 AC: 5 AN: 143870 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000363

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

GnomAD2 exomes AF: 0.000150 AC: 29 AN: 193088 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000203

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000408 AC: 59 AN: 1446130 Hom.: 0 Cov.: 35 AF XY: 0.0000486 AC XY: 35 AN XY: 719454

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

African (AFR) AF: 0.00 AC: 0 AN: 32088

American (AMR) AF: 0.00105 AC: 41 AN: 39218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25002

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39554

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000812 AC: 9 AN: 1107770

Other (OTH) AF: 0.0000335 AC: 2 AN: 59640

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000111022), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000348 AC: 5 AN: 143870 Hom.: 0 Cov.: 28 AF XY: 0.0000431 AC XY: 3 AN XY: 69642

African (AFR) AF: 0.00 AC: 0 AN: 37936

American (AMR) AF: 0.000363 AC: 5 AN: 13780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 4920

South Asian (SAS) AF: 0.00 AC: 0 AN: 4246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9944

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66564

Other (OTH) AF: 0.00 AC: 0 AN: 1886

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.000116 AC: 14

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	0.084
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.6
DANN	Benign	0.97
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.27
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.13
Sift	Benign	0.086	T
Sift4G	Benign	0.13	T
Polyphen		0.21	B
Vest4		0.16
MutPred		0.55		Loss of MoRF binding (P = 0.014)
MVP		0.27
MPC		1.2
ClinPred		0.062	T
GERP RS		-1.3
Varity_R		0.069
gMVP		0.19
Mutation Taster		=100/0	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: rs778525180; hg19: chr12-7980269; COSMIC: COSV61585472; COSMIC: COSV61585472;