12-40028449-C-T

Variant names:

• chr12-40028449-C-T
• rs759358485
• NM_052885.4:c.777G>A

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.777G>A​(p.Leu259Leu) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• 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]

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 (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052885.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A13	NM_052885.4	MANE Select	c.777G>A	p.Leu259Leu	synonymous	Exon 3 of 10	NP_443117.3	Q96QE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A13	ENST00000280871.9	TSL:1 MANE Select	c.777G>A	p.Leu259Leu	synonymous	Exon 3 of 10	ENSP00000280871.4	Q96QE2
	SLC2A13	ENST00000380858.1	TSL:1	c.777G>A	p.Leu259Leu	synonymous	Exon 3 of 4	ENSP00000370239.1	E9PE47
	SLC2A13	ENST00000957640.1		c.777G>A	p.Leu259Leu	synonymous	Exon 3 of 11	ENSP00000627699.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251178 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.6
DANN	Benign	0.74
PhyloP100		1.2

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

Other links and lift over

dbSNP: rs759358485; hg19: chr12-40422251;