12-7930596-A-T

Position:

• chr12-7930596-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006931.3(SLC2A3):​c.557T>A​(p.Leu186Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 6.64

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A3	NM_006931.3	c.557T>A	p.Leu186Gln	missense_variant	5/10	ENST00000075120.12	NP_008862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A3	ENST00000075120.12	c.557T>A	p.Leu186Gln	missense_variant	5/10	1	NM_006931.3	ENSP00000075120	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

May 07, 2024

The c.557T>A (p.L186Q) alteration is located in exon 5 (coding exon 5) of the SLC2A3 gene. This alteration results from a T to A substitution at nucleotide position 557, causing the leucine (L) at amino acid position 186 to be replaced by a glutamine (Q). 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	0.35
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.065	D
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.60	P
Vest4		0.71
MutPred		0.61		Gain of catalytic residue at W184 (P = 0);
MVP		0.62
MPC		1.2
ClinPred		0.96	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.31

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: chr12-8083192;