rs753861463

Variant names:

• chr12-39764815-C-G
• rs753861463
• NM_052885.4:c.1489G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-39764815-C-G
• chr12-39764815-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_052885.4(SLC2A13):​c.1489G>C​(p.Ala497Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A497T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC2A13 NM_052885.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

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.1489G>C	p.Ala497Pro	missense	Exon 8 of 10	NP_443117.3	Q96QE2
	REDIC1	NR_135051.2		n.2225+6C>G		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A13	ENST00000280871.9	TSL:1 MANE Select	c.1489G>C	p.Ala497Pro	missense	Exon 8 of 10	ENSP00000280871.4	Q96QE2
	REDIC1	ENST00000468200.2	TSL:1	n.*794+6C>G		splice_region intron	N/A	ENSP00000473371.1	Q86WS4-3
	SLC2A13	ENST00000957640.1		c.1660G>C	p.Ala554Pro	missense	Exon 9 of 11	ENSP00000627699.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460392 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726500

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111170

Other (OTH) AF: 0.00 AC: 0 AN: 60278

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.44	T
PhyloP100		7.3
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.32
Sift	Benign	0.032	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.63		Loss of catalytic residue at A497 (P = 0.0456)
MVP		0.78
MPC		0.95
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.83
gMVP		0.98
Mutation Taster		=4/96	disease causing

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: rs753861463; hg19: chr12-40158617;