11-47410177-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001128225.3(SLC39A13):c.83A>G(p.Glu28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,613,612 control chromosomes in the GnomAD database, including 793,255 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69401 hom., cov: 33)

Exomes 𝑓: 0.99 ( 723854 hom. )

Consequence

SLC39A13
NM_001128225.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.448

Publications

31 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.071712E-7).

BP6

Variant 11-47410177-A-G is Benign according to our data. Variant chr11-47410177-A-G is described in ClinVar as Benign. ClinVar VariationId is 403458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC39A13	NM_001128225.3	MANE Select	c.83A>G	p.Glu28Gly	missense	Exon 2 of 10	NP_001121697.2
SLC39A13	NM_001441271.1		c.83A>G	p.Glu28Gly	missense	Exon 3 of 11	NP_001428200.1
SLC39A13	NM_152264.5		c.83A>G	p.Glu28Gly	missense	Exon 2 of 10	NP_689477.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.83A>G	p.Glu28Gly	missense	Exon 2 of 10	ENSP00000354689.4
SLC39A13	ENST00000354884.8	TSL:1	c.83A>G	p.Glu28Gly	missense	Exon 2 of 10	ENSP00000346956.4
SLC39A13	ENST00000533076.5	TSL:2	c.83A>G	p.Glu28Gly	missense	Exon 2 of 11	ENSP00000434290.1

Frequencies

GnomAD3 genomes

AF:

0.952

AC:

144885

AN:

152132

Hom.:

69384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.833

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.965

GnomAD2 exomes

AF:

0.988

AC:

246022

AN:

248998

AF XY:

0.991

show subpopulations

Gnomad AFR exome

AF:

0.830

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

0.999

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.995

GnomAD4 exome

AF:

0.995

AC:

1453945

AN:

1461362

Hom.:

723854

Cov.:

AF XY:

0.996

AC XY:

723849

AN XY:

726988

show subpopulations

African (AFR)

AF:

0.820

AC:

27448

AN:

33478

American (AMR)

AF:

0.992

AC:

44357

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

26097

AN:

26120

East Asian (EAS)

AF:

1.00

AC:

39700

AN:

39700

South Asian (SAS)

AF:

1.00

AC:

86220

AN:

86250

European-Finnish (FIN)

AF:

1.00

AC:

52970

AN:

52970

Middle Eastern (MID)

AF:

0.993

AC:

5726

AN:

5766

European-Non Finnish (NFE)

AF:

1.00

AC:

1111730

AN:

1111976

Other (OTH)

AF:

0.989

AC:

59697

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

401

803

1204

1606

2007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21664

43328

64992

86656

108320

<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:

0.952

AC:

144954

AN:

152250

Hom.:

69401

Cov.:

AF XY:

0.954

AC XY:

71022

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.833

AC:

34562

AN:

41512

American (AMR)

AF:

0.985

AC:

15073

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

3467

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5158

AN:

5158

South Asian (SAS)

AF:

0.999

AC:

4825

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10630

AN:

10630

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

67997

AN:

68026

Other (OTH)

AF:

0.965

AC:

2041

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

311

623

934

1246

1557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.988

Hom.:

81726

Bravo

AF:

0.946

TwinsUK

AF:

0.999

AC:

3706

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.837

AC:

3678

ESP6500EA

AF:

0.999

AC:

8573

ExAC

AF:

0.984

AC:

119340

Asia WGS

AF:

0.984

AC:

3423

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Ehlers-Danlos syndrome, spondylocheirodysplastic type

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.0064

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.11

MetaRNN

Benign

6.1e-7

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.97

PhyloP100

0.45

PrimateAI

Benign

0.40

PROVEAN

Benign

0.89

REVEL

Benign

0.088

Sift

Benign

1.0

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.040

MPC

0.39

ClinPred

0.00021

GERP RS

4.2

PromoterAI

0.0085

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.042

gMVP

0.60

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over