12-7935631-T-C

Variant names:

• chr12-7935631-T-C
• rs2244822
• NM_006931.3:c.15+389A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006931.3(SLC2A3):​c.15+389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,876 control chromosomes in the GnomAD database, including 6,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6757 hom., cov: 32)
• Consequence: SLC2A3 NM_006931.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 4 publications found

Genes affected

SLC2A3 (HGNC:11007): (solute carrier family 2 member 3) Enables dehydroascorbic acid transmembrane transporter activity; glucose binding activity; and glucose transmembrane transporter activity. Involved in glucose import across plasma membrane and transport across blood-brain barrier. Is integral component of plasma membrane. Biomarker of Alzheimer's disease; acanthosis nigricans; diabetes mellitus; and type 2 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

SLC2A3 Gene-Disease associations (from GenCC):

• Huntington disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006931.3. 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
	SLC2A3	NM_006931.3	MANE Select	c.15+389A>G		intron	N/A	NP_008862.1	P11169

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A3	ENST00000075120.12	TSL:1 MANE Select	c.15+389A>G		intron	N/A	ENSP00000075120.7	P11169
	SLC2A3	ENST00000486749.5	TSL:1	n.148+389A>G		intron	N/A
	SLC2A3	ENST00000926562.1		c.15+389A>G		intron	N/A	ENSP00000596621.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44839 AN: 151756 Hom.: 6754 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.296 AC: 44892 AN: 151876 Hom.: 6757 Cov.: 32 AF XY: 0.300 AC XY: 22293 AN XY: 74234

African (AFR) AF: 0.286 AC: 11839 AN: 41438

American (AMR) AF: 0.292 AC: 4449 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3462

East Asian (EAS) AF: 0.524 AC: 2703 AN: 5160

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4816

European-Finnish (FIN) AF: 0.279 AC: 2941 AN: 10538

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18885 AN: 67904

Other (OTH) AF: 0.302 AC: 638 AN: 2112

Alfa AF: 0.280 Hom.: 4231

Bravo AF: 0.292

Asia WGS AF: 0.440 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.52
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2244822; hg19: chr12-8088227;