12-39760097-A-G

Variant names:

• chr12-39760097-A-G
• NM_052885.4:c.1876T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052885.4(SLC2A13):​c.1876T>C​(p.Tyr626His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC2A13 NM_052885.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

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]

REDIC1 (HGNC:26846): (regulator of DNA class I crossover intermediates 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08829492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A13	NM_052885.4	c.1876T>C	p.Tyr626His	missense_variant	Exon 10 of 10	ENST00000280871.9	NP_443117.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A13	ENST00000280871.9	c.1876T>C	p.Tyr626His	missense_variant	Exon 10 of 10	1	NM_052885.4	ENSP00000280871.4
REDIC1	ENST00000468200.2	n.*725-4643A>G		intron_variant	Intron 15 of 18	1		ENSP00000473371.1

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

Dec 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1876T>C (p.Y626H) alteration is located in exon 10 (coding exon 10) of the SLC2A13 gene. This alteration results from a T to C substitution at nucleotide position 1876, causing the tyrosine (Y) at amino acid position 626 to be replaced by a histidine (H). 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	0.14
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.082
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.20	N
PhyloP100		4.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.19
Sift	Benign	0.25	T
Sift4G	Benign	0.53	T
Polyphen		0.0020	B
Vest4		0.14
MutPred		0.31		Gain of disorder (P = 0.0299);
MVP		0.13
MPC		0.29
ClinPred		0.53	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.50
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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

hg19: chr12-40153899;