chr12-40048081-G-T

Variant names:

• chr12-40048081-G-T
• NM_052885.4:c.686C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_052885.4(SLC2A13):​c.686C>A​(p.Ala229Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,856 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.

• 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: 4.81

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A13	NM_052885.4	c.686C>A	p.Ala229Asp	missense_variant	Exon 2 of 10	ENST00000280871.9	NP_443117.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A13	ENST00000280871.9	c.686C>A	p.Ala229Asp	missense_variant	Exon 2 of 10	1	NM_052885.4	ENSP00000280871.4
SLC2A13	ENST00000380858.1	c.686C>A	p.Ala229Asp	missense_variant	Exon 2 of 4	1		ENSP00000370239.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459856 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Uncertain	0.48
Sift	Benign	0.057	T;D
Sift4G	Benign	0.077	T;D
Polyphen		0.99	D;P
Vest4		0.90
MutPred		0.92		Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP		0.80
MPC		0.96
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.54
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-40441883;