chr12-7933487-C-A

Variant names:

• chr12-7933487-C-A
• rs7976243
• NM_006931.3:c.108+323G>T

Variant summary

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

The NM_006931.3(SLC2A3):​c.108+323G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 456,834 control chromosomes in the GnomAD database, including 22,329 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 0.29 (6753 hom., cov: 32)
  • Exomes 𝑓: 0.31 (15576 hom.)
• Consequence: SLC2A3 NM_006931.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 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.108+323G>T		intron	N/A	NP_008862.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A3	ENST00000075120.12	TSL:1 MANE Select	c.108+323G>T		intron	N/A	ENSP00000075120.7
	SLC2A3	ENST00000486749.5	TSL:1	n.241+323G>T		intron	N/A
	SLC2A3	ENST00000926562.1		c.141+323G>T		intron	N/A	ENSP00000596621.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44744 AN: 151764 Hom.: 6753 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.312 AC: 95214 AN: 304950 Hom.: 15576 Cov.: 3 AF XY: 0.318 AC XY: 51012 AN XY: 160324

African (AFR) AF: 0.283 AC: 2808 AN: 9930

American (AMR) AF: 0.282 AC: 3262 AN: 11560

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 3276 AN: 9608

East Asian (EAS) AF: 0.520 AC: 10733 AN: 20638

South Asian (SAS) AF: 0.405 AC: 12393 AN: 30632

European-Finnish (FIN) AF: 0.298 AC: 5068 AN: 16996

Middle Eastern (MID) AF: 0.325 AC: 432 AN: 1328

European-Non Finnish (NFE) AF: 0.278 AC: 51746 AN: 186236

Other (OTH) AF: 0.305 AC: 5496 AN: 18022

GnomAD4 genome AF: 0.295 AC: 44789 AN: 151884 Hom.: 6753 Cov.: 32 AF XY: 0.299 AC XY: 22211 AN XY: 74208

African (AFR) AF: 0.284 AC: 11759 AN: 41436

American (AMR) AF: 0.291 AC: 4442 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2713 AN: 5148

South Asian (SAS) AF: 0.409 AC: 1971 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2931 AN: 10542

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.277 AC: 18812 AN: 67904

Other (OTH) AF: 0.304 AC: 643 AN: 2114

Alfa AF: 0.280 Hom.: 25307

Bravo AF: 0.292

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.73
DANN	Benign	0.53
PhyloP100		-0.073
Mutation Taster		=100/0	polymorphism (auto)

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: rs7976243; hg19: chr12-8086083;