rs201737691

Variant names:

• chr12-7922826-C-A
• rs201737691
• NM_006931.3:c.1267G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-7922826-C-A
• chr12-7922826-C-G
• chr12-7922826-C-T

Variant summary

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

The NM_006931.3(SLC2A3):​c.1267G>T​(p.Ala423Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A423T) 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: 1.35
• Publications: 6 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1267G>T	p.Ala423Ser	missense	Exon 9 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.1267G>T	p.Ala423Ser	missense	Exon 9 of 10	ENSP00000075120.7	P11169
	SLC2A3	ENST00000486749.5	TSL:1	n.2008G>T		non_coding_transcript_exon	Exon 8 of 9
	SLC2A3	ENST00000926562.1		c.1300G>T	p.Ala434Ser	missense	Exon 9 of 10	ENSP00000596621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.45
MutPred		0.63		Gain of catalytic residue at L418 (P = 0)
MVP		0.61
MPC		1.7
ClinPred		0.88	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.74
gMVP		0.38
Mutation Taster		=70/30	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: rs201737691; hg19: chr12-8075422; COSMIC: COSV50002302; COSMIC: COSV50002302;