12-7929734-T-C

Position:

• chr12-7929734-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000075120.12(SLC2A3):​c.811A>G​(p.Ile271Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I271T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC2A3 ENST00000075120.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.118

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12560919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A3	NM_006931.3	c.811A>G	p.Ile271Val	missense_variant	6/10	ENST00000075120.12	NP_008862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A3	ENST00000075120.12	c.811A>G	p.Ile271Val	missense_variant	6/10	1	NM_006931.3	ENSP00000075120	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Sep 07, 2022

The c.811A>G (p.I271V) alteration is located in exon 6 (coding exon 6) of the SLC2A3 gene. This alteration results from a A to G substitution at nucleotide position 811, causing the isoleucine (I) at amino acid position 271 to be replaced by a valine (V). 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	Benign	0.083
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.21
Sift	Benign	0.24	T
Sift4G	Benign	0.22	T
Polyphen		0.012	B
Vest4		0.30
MutPred		0.52		Gain of catalytic residue at I271 (P = 5e-04);
MVP		0.20
MPC		0.44
ClinPred		0.088	T
GERP RS		-1.2
Varity_R		0.11
gMVP		0.16

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: chr12-8082330;