rs35741412

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001128225.3(SLC39A13):c.119G>A(p.Arg40Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,613,426 control chromosomes in the GnomAD database, including 370 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 32)

Exomes 𝑓: 0.020 ( 350 hom. )

Consequence

SLC39A13
NM_001128225.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.50

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004864067).

BP6

Variant 11-47410213-G-A is Benign according to our data. Variant chr11-47410213-G-A is described in ClinVar as [Benign]. Clinvar id is 289730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47410213-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.012 (1824/152304) while in subpopulation NFE AF= 0.0203 (1379/68016). AF 95% confidence interval is 0.0194. There are 20 homozygotes in gnomad4. There are 809 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A13	NM_001128225.3 linkuse as main transcript	c.119G>A	p.Arg40Gln	missense_variant	2/10	ENST00000362021.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A13	ENST00000362021.9 linkuse as main transcript	c.119G>A	p.Arg40Gln	missense_variant	2/10	1	NM_001128225.3	P4	Q96H72-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1826

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0132

AC:

3312

AN:

250168

Hom.:

AF XY:

0.0131

AC XY:

1773

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00442

Gnomad AMR exome

AF:

0.00596

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.00856

Gnomad NFE exome

AF:

0.0229

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0196

AC:

28693

AN:

1461122

Hom.:

350

Cov.:

AF XY:

0.0192

AC XY:

13948

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00356

Gnomad4 AMR exome

AF:

0.00597

Gnomad4 ASJ exome

AF:

0.00946

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00289

Gnomad4 FIN exome

AF:

0.00932

Gnomad4 NFE exome

AF:

0.0237

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.0120

AC:

1824

AN:

152304

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

809

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00337

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00602

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0124

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0210

AC:

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.0249

AC:

214

ExAC

AF:

0.0145

AC:

1763

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0205

EpiControl

AF:

0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	This variant is associated with the following publications: (PMID: 26091878, 27211562, 26925801) -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	SLC39A13: BP4, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 06, 2016

- -

Ehlers-Danlos syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 16, 2022

- -

Ehlers-Danlos syndrome, spondylocheirodysplastic type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0071

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

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.85

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

MetaRNN

Benign

0.0049

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.27

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

REVEL

Benign

0.10

Sift

Benign

0.23

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

Sift4G

Benign

0.57

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

Polyphen

0.019, 0.013, 0.059

.;.;.;.;B;B;.;.;B

Vest4

0.094

MPC

0.39

ClinPred

0.0060

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.043

gMVP

0.40

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