Genetic Variant SLC13A2:p.Ile550Val (chr17-28497138-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003984.4(SLC13A2):c.1648A>G(p.Ile550Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,718 control chromosomes in the GnomAD database, including 120,054 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 15272 hom., cov: 32)

Exomes 𝑓: 0.37 ( 104782 hom. )

Consequence

SLC13A2
NM_003984.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.454

Publications

38 publications found

Variant links:

Genes affected

SLC13A2 (HGNC:10917): (solute carrier family 13 member 2) The protein encoded by this gene is a sodium-coupled citrate transporter that is regulated by the chaperone activity of cyclophilin b. The encoded protein may play a role in the formation of kidney stones. [provided by RefSeq, Oct 2016]

SLC13A2 links:

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

RSKR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.599328E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A2	NM_003984.4 link	c.1648A>G	p.Ile550Val	missense_variant	Exon 12 of 12	ENST00000314669.10	NP_003975.1	Q13183-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A2	ENST00000314669.10 link	c.1648A>G	p.Ile550Val	missense_variant	Exon 12 of 12	1	NM_003984.4	ENSP00000316202.6		Q13183-1

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

65976

AN:

151796

Hom.:

15223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.425

GnomAD2 exomes

AF:

0.405

AC:

101654

AN:

251160

AF XY:

0.397

show subpopulations

Gnomad AFR exome

AF:

0.598

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.374

AC:

546171

AN:

1461804

Hom.:

104782

Cov.:

AF XY:

0.374

AC XY:

271771

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.600

AC:

20089

AN:

33478

American (AMR)

AF:

0.521

AC:

23289

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

9785

AN:

26130

East Asian (EAS)

AF:

0.408

AC:

16209

AN:

39700

South Asian (SAS)

AF:

0.440

AC:

37912

AN:

86254

European-Finnish (FIN)

AF:

0.363

AC:

19375

AN:

53412

Middle Eastern (MID)

AF:

0.459

AC:

2645

AN:

5768

European-Non Finnish (NFE)

AF:

0.354

AC:

393437

AN:

1111952

Other (OTH)

AF:

0.388

AC:

23430

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

19249

38497

57746

76994

96243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12832

25664

38496

51328

64160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.435

AC:

66075

AN:

151914

Hom.:

15272

Cov.:

AF XY:

0.434

AC XY:

32217

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.594

AC:

24574

AN:

41390

American (AMR)

AF:

0.480

AC:

7330

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1311

AN:

3466

East Asian (EAS)

AF:

0.370

AC:

1906

AN:

5148

South Asian (SAS)

AF:

0.440

AC:

2116

AN:

4812

European-Finnish (FIN)

AF:

0.363

AC:

3845

AN:

10586

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23668

AN:

67928

Other (OTH)

AF:

0.428

AC:

903

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1858

3716

5575

7433

9291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.383

Hom.:

38918

Bravo

AF:

0.448

TwinsUK

AF:

0.351

AC:

1303

ALSPAC

AF:

0.360

AC:

1387

ESP6500AA

AF:

0.579

AC:

2552

ESP6500EA

AF:

0.346

AC:

2975

ExAC

AF:

0.404

AC:

49035

Asia WGS

AF:

0.416

AC:

1446

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.031

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.37

T;T

MetaRNN

Benign

0.0000056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

.;N

PhyloP100

0.45

PrimateAI

Benign

0.32

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.027

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.023

MPC

0.23

ClinPred

0.0027

GERP RS

3.2

Varity_R

0.058

gMVP

0.39

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over