12-7921469-C-A

Variant names:

• chr12-7921469-C-A
• rs776087207
• NM_006931.3:c.1435G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006931.3(SLC2A3):​c.1435G>T​(p.Gly479Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G479S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A3 NM_006931.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08628926).

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.1435G>T	p.Gly479Cys	missense	Exon 10 of 10	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.1435G>T	p.Gly479Cys	missense	Exon 10 of 10	ENSP00000075120.7	P11169
	SLC2A3	ENST00000486749.5	TSL:1	n.2176G>T		non_coding_transcript_exon	Exon 9 of 9
	SLC2A3	ENST00000926562.1		c.1468G>T	p.Gly490Cys	missense	Exon 10 of 10	ENSP00000596621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.6
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.49
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Benign	0.048	D
Sift4G	Benign	0.16	T
Polyphen		0.32	B
Vest4		0.16
MutPred		0.35		Gain of catalytic residue at K477 (P = 0.0511)
MVP		0.18
MPC		1.4
ClinPred		0.24	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.072
gMVP		0.53
Mutation Taster		=98/2	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: rs776087207; hg19: chr12-8074065;