12-39864768-C-G

Variant names:

• chr12-39864768-C-G
• rs1943859446
• NM_052885.4:c.1313G>C

Variant summary

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

The NM_052885.4(SLC2A13):​c.1313G>C​(p.Arg438Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC2A13 NM_052885.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

Genes affected

SLC2A13 (HGNC:15956): (solute carrier family 2 member 13) Enables ATPase binding activity; myo-inositol:proton symporter activity; and protease binding activity. Involved in myo-inositol transport and positive regulation of amyloid-beta formation. Is integral component of plasma membrane. Part of cell body; cell periphery; and cell projection. [provided by Alliance of Genome Resources, Apr 2022]

C12orf40 (HGNC:26846): (regulator of DNA class I crossover intermediates 1)

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=0.14217678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A13	NM_052885.4	c.1313G>C	p.Arg438Thr	missense_variant	Exon 6 of 10	ENST00000280871.9	NP_443117.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A13	ENST00000280871.9	c.1313G>C	p.Arg438Thr	missense_variant	Exon 6 of 10	1	NM_052885.4	ENSP00000280871.4
C12orf40	ENST00000468200.2	n.*999-42866C>G		intron_variant	Intron 18 of 18	1		ENSP00000473371.1
SLC2A13	ENST00000465517.1	n.199G>C		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1313G>C (p.R438T) alteration is located in exon 6 (coding exon 6) of the SLC2A13 gene. This alteration results from a G to C substitution at nucleotide position 1313, causing the arginine (R) at amino acid position 438 to be replaced by a threonine (T). 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	0.072
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.20
Sift	Benign	0.56	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.60		Gain of glycosylation at R438 (P = 0.085);
MVP		0.093
MPC		0.32
ClinPred		0.26	T
GERP RS		4.0
Varity_R		0.051
gMVP		0.79

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

LitVar

Other links and lift over

dbSNP: rs1943859446; hg19: chr12-40258570;