12-39764542-TGC-CGA

Variant names:

• chr12-39764542-TGC-CGA
• NM_052885.4:c.1636_1638delGCAinsTCG
• SLC2A13 p.Ala546Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_052885.4(SLC2A13):​c.1636_1638delGCAinsTCG​(p.Ala546Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC2A13 NM_052885.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.52
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1636_1638delGCAinsTCG	p.Ala546Ser	missense	N/A	NP_443117.3	Q96QE2
	REDIC1	NR_135051.2		n.2156-198_2156-196delTGCinsCGA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A13	ENST00000280871.9	TSL:1 MANE Select	c.1636_1638delGCAinsTCG	p.Ala546Ser	missense	N/A	ENSP00000280871.4	Q96QE2
	REDIC1	ENST00000468200.2	TSL:1	n.*725-198_*725-196delTGCinsCGA		intron	N/A	ENSP00000473371.1	Q86WS4-3
	SLC2A13	ENST00000957640.1		c.1807_1809delGCAinsTCG	p.Ala603Ser	missense	N/A	ENSP00000627699.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-40158344;