11-47412022-C-T

Position:

chr11-47412022-C-T

Variant summary

Our verdict is Benign. Variant got -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).

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:8

Conservation

PhyloP100: 2.60

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 196579.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=2, Uncertain_significance=2}. Variant chr11-47412022-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A13	NM_001128225.3 linkuse as main transcript	c.398C>T	p.Thr133Met	missense_variant	3/10	ENST00000362021.9	NP_001121697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A13	ENST00000362021.9 linkuse as main transcript	c.398C>T	p.Thr133Met	missense_variant	3/10	1	NM_001128225.3	ENSP00000354689	P4	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

GnomAD3 exomes

AF:

0.00224

AC:

540

AN:

241562

Hom.:

AF XY:

0.00230

AC XY:

302

AN XY:

131306

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 SAS exome

AF:

0.00171

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

Gnomad4 AFR exome

AF:

0.000718

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00231

Gnomad4 EAS exome

AF:

0.000530

Gnomad4 SAS exome

AF:

0.00219

Gnomad4 FIN exome

AF:

0.000358

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.00202

AC:

308

AN:

152374

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00345

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00343

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:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:4

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 29, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 27, 2023	See Variant Classification Assertion Criteria. -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	SLC39A13: BS2 -

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

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 10, 2014

- -

SLC39A13-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 19, 2021

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

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 17, 2022

- -

Ehlers-Danlos syndrome, spondylocheirodysplastic type

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 17, 2022

- -

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

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;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over