rs148291843

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.439C>G(p.Gln147Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00265 in 1,614,098 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 8 hom. )

Consequence

SLC39A13
NM_001128225.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:10

Conservation

PhyloP100: 3.85

Publications

11 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=0.009007037).

BP6

Variant 11-47412369-C-G is Benign according to our data. Variant chr11-47412369-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 287155.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A13	NM_001128225.3 link	c.439C>G	p.Gln147Glu	missense_variant	Exon 4 of 10	ENST00000362021.9	NP_001121697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A13	ENST00000362021.9 link	c.439C>G	p.Gln147Glu	missense_variant	Exon 4 of 10	1	NM_001128225.3	ENSP00000354689.4

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

313

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00298

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00170

AC:

425

AN:

250280

AF XY:

0.00179

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00182

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00271

AC:

3959

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

1943

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33478

American (AMR)

AF:

0.000850

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00306

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00324

AC:

3601

AN:

1111930

Other (OTH)

AF:

0.00255

AC:

154

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

250

500

750

1000

1250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.00205

AC:

313

AN:

152360

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41584

American (AMR)

AF:

0.00379

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00298

AC:

203

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00270

Hom.:

Bravo

AF:

0.00193

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00152

AC:

184

EpiCase

AF:

0.00371

EpiControl

AF:

0.00231

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:10

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Apr 07, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC39A13: BP4, BS2 -

Jun 26, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Mar 31, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2025

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: SLC39A13 c.439C>G (p.Gln147Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 250280 control chromosomes, predominantly at a frequency of 0.0028 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database 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.439C>G 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: 287155). Based on the evidence outlined above, the variant was classified as likely benign. -

Ehlers-Danlos syndrome, spondylocheirodysplastic type

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 30, 2021

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC39A13 NM_152264.4 exon 4 p.Gln147Glu (c.439C>G): This variant has not been reported in the literature but is present in 0.3% (203/68032) of European alleles, including 3 homozygotes, in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/11-47412369-C-G?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as likely benign (Variation ID: 287155). Evolutionary conservation for this variant is unclear. Computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign. -

Inborn genetic diseases

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.439C>G (p.Q147E) alteration is located in exon 4 (coding exon 3) of the SLC39A13 gene. This alteration results from a C to G substitution at nucleotide position 439, causing the glutamine (Q) at amino acid position 147 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

SLC39A13-related disorder

Benign:1

Oct 23, 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

Jun 13, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.011

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

Eigen

Benign

-0.16

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

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

M_CAP

Benign

0.0094

MetaRNN

Benign

0.0090

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.51

.;.;.;N;N;.;.

PhyloP100

3.9

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.91

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

REVEL

Benign

0.12

Sift

Benign

1.0

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

Sift4G

Benign

0.54

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

Polyphen

0.084, 0.035, 0.93

.;.;.;B;B;.;P

Vest4

0.41

MVP

0.39

MPC

0.46

ClinPred

0.022

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.29

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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