12-7931289-T-A

Position:

• chr12-7931289-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006931.3(SLC2A3):​c.466A>T​(p.Thr156Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC2A3 NM_006931.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A3	NM_006931.3	c.466A>T	p.Thr156Ser	missense_variant	4/10	ENST00000075120.12	NP_008862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A3	ENST00000075120.12	c.466A>T	p.Thr156Ser	missense_variant	4/10	1	NM_006931.3	ENSP00000075120	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.466A>T (p.T156S) alteration is located in exon 4 (coding exon 4) of the SLC2A3 gene. This alteration results from a A to T substitution at nucleotide position 466, causing the threonine (T) at amino acid position 156 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.67	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.50
Sift	Benign	0.052	T;D
Sift4G	Benign	0.073	T;.
Polyphen		0.97	D;.
Vest4		0.77
MutPred		0.50		Gain of catalytic residue at N158 (P = 8e-04);.;
MVP		0.40
MPC		0.73
ClinPred		0.96	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-8083885;