dbSNP rs781067627: SLC2A13:p.Asn556Lys (chr12-39764512-A-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_052885.4(SLC2A13):c.1668T>G(p.Asn556Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,611,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SLC2A13
NM_052885.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.362

Publications

0 publications found

Variant links:

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]

SLC2A13 links:

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

REDIC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A13	NM_052885.4 link	c.1668T>G	p.Asn556Lys	missense_variant	Exon 9 of 10	ENST00000280871.9	NP_443117.3	Q96QE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A13	ENST00000280871.9 link	c.1668T>G	p.Asn556Lys	missense_variant	Exon 9 of 10	1	NM_052885.4	ENSP00000280871.4		Q96QE2
REDIC1	ENST00000468200.2 link	n.*725-228A>C		intron_variant	Intron 15 of 18	1		ENSP00000473371.1		Q86WS4-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249074

AF XY:

0.00

show subpopulations

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:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1458966

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33266

American (AMR)

AF:

0.00

AC:

AN:

44210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

85406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111020

Other (OTH)

AF:

0.0000166

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1668T>G (p.N556K) alteration is located in exon 9 (coding exon 9) of the SLC2A13 gene. This alteration results from a T to G substitution at nucleotide position 1668, causing the asparagine (N) at amino acid position 556 to be replaced by a lysine (K). 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

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.97

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.44

MutationAssessor

Pathogenic

4.1

PhyloP100

0.36

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.3

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.98

MutPred

0.87

Gain of methylation at N556 (P = 0.0037);

MVP

0.66

MPC

0.90

ClinPred

1.0

GERP RS

-1.3

Varity_R

0.81

gMVP

0.98

Mutation Taster

=15/85

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs781067627

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over