chr12-7933487-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006931.3(SLC2A3):​c.108+323G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 306,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: SLC2A3 NM_006931.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A3	NM_006931.3	c.108+323G>C		intron_variant	Intron 2 of 9	ENST00000075120.12	NP_008862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A3	ENST00000075120.12	c.108+323G>C		intron_variant	Intron 2 of 9	1	NM_006931.3	ENSP00000075120.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000653 AC: 2 AN: 306270 Hom.: 0 Cov.: 3 AF XY: 0.0000124 AC XY: 2 AN XY: 161012

African (AFR) AF: 0.00 AC: 0 AN: 9958

American (AMR) AF: 0.00 AC: 0 AN: 11590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9636

East Asian (EAS) AF: 0.00 AC: 0 AN: 20730

South Asian (SAS) AF: 0.00 AC: 0 AN: 30754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1338

European-Non Finnish (NFE) AF: 0.0000107 AC: 2 AN: 187048

Other (OTH) AF: 0.00 AC: 0 AN: 18128

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.23
PhyloP100		-0.073

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;