11-47412022-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001128225.3(SLC39A13):c.398C>T(p.Thr133Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,611,382 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T133T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 20 hom. )

Consequence

SLC39A13
NM_001128225.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:9

Conservation

PhyloP100: 2.60

Publications

16 publications found

Variant links:

Genes affected

SLC39A13 (HGNC:20859): (solute carrier family 39 member 13) This gene encodes a member of the LIV-1 subfamily of the ZIP transporter family. The encoded transmembrane protein functions as a zinc transporter. Mutations in this gene have been associated with the spondylocheiro dysplastic form of Ehlers-Danlos syndrome. Alternate transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

SLC39A13 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome, spondylocheirodysplastic type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P, Orphanet, Genomics England PanelApp
spondyloepimetaphyseal dysplasia-abnormal dentition syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

SLC39A13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009471446).

BP6

Variant 11-47412022-C-T is Benign according to our data. Variant chr11-47412022-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 196579.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A13	NM_001128225.3 link	c.398C>T	p.Thr133Met	missense_variant	Exon 3 of 10	ENST00000362021.9	NP_001121697.2	Q96H72-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A13	ENST00000362021.9 link	c.398C>T	p.Thr133Met	missense_variant	Exon 3 of 10	1	NM_001128225.3	ENSP00000354689.4		Q96H72-1

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

308

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00345

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00224

AC:

540

AN:

241562

AF XY:

0.00230

show subpopulations

Gnomad AFR exome

AF:

0.000458

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.00244

Gnomad EAS exome

AF:

0.000439

Gnomad FIN exome

AF:

0.000198

Gnomad NFE exome

AF:

0.00359

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00324

AC:

4726

AN:

1459008

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

2348

AN XY:

725544

show subpopulations

African (AFR)

AF:

0.000718

AC:

AN:

33432

American (AMR)

AF:

0.00135

AC:

AN:

44376

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

25986

East Asian (EAS)

AF:

0.000530

AC:

AN:

39652

South Asian (SAS)

AF:

0.00219

AC:

188

AN:

85652

European-Finnish (FIN)

AF:

0.000358

AC:

AN:

53106

Middle Eastern (MID)

AF:

0.00215

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.00375

AC:

4169

AN:

1110976

Other (OTH)

AF:

0.00287

AC:

173

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

274

549

823

1098

1372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<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:

0.00202

AC:

308

AN:

152374

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74524

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41582

American (AMR)

AF:

0.00144

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00345

AC:

235

AN:

68036

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00345

Hom.:

Bravo

AF:

0.00212

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00361

AC:

ExAC

AF:

0.00236

AC:

286

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:9

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:4

Jan 29, 2015

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC39A13: BS2 -

Mar 18, 2025

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Cutis laxa;C0011644:Scleroderma;C0026267:Mitral valve prolapse;C0027092:Myopia;C4021790:Abnormality of the skeletal system;C4025596:Abnormality of connective tissue

Uncertain:1

Jan 10, 2014

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 07, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: SLC39A13 c.398C>T (p.Thr133Met) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0031 in 1604598 control chromosomes in the gnomAD database (v4.1 dataset), including 20 homozygotes. The observed variant frequency is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC39A13 causing Ehlers-Danlos syndrome, spondylocheirodysplastic type phenotype (0.0011). To our knowledge, no occurrence of c.398C>T in individuals affected with Ehlers-Danlos syndrome, spondylocheirodysplastic type and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 196579). Based on the evidence outlined above, the variant was classified as benign. -

SLC39A13-related disorder

Benign:1

Aug 19, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Ehlers-Danlos syndrome

Benign:1

Jul 17, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, spondylocheirodysplastic type

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Connective tissue disorder

Benign:1

Jul 17, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

T;T;.;T;T;.;.;.;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.062

MetaRNN

Benign

0.0095

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.3

.;.;.;.;M;M;.;.;.

PhyloP100

2.6

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.14

T;D;T;T;T;T;T;D;T

Sift4G

Benign

0.097

T;T;T;T;T;T;T;T;T

Polyphen

0.80, 0.76, 1.0

.;.;.;.;P;P;.;.;D

Vest4

0.64

MVP

0.64

MPC

0.60

ClinPred

0.021

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.33

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over