rs2280838

Variant names:

Variant summary

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

The NM_130849.4(SLC39A4):c.172G>A(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,594,344 control chromosomes in the GnomAD database, including 239,184 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20470 hom., cov: 33)

Exomes 𝑓: 0.55 ( 218714 hom. )

Consequence

SLC39A4
NM_130849.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.20

Publications

34 publications found

Variant links:

Genes affected

SLC39A4 (HGNC:17129): (solute carrier family 39 member 4) This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. Mutations in this gene result in acrodermatitis enteropathica. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

SLC39A4 Gene-Disease associations (from GenCC):

acrodermatitis enteropathica
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

SLC39A4 links:

LOC124902041 (HGNC:):

LOC124902041 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=6.3947305E-6).

BP6

Variant 8-144416618-C-T is Benign according to our data. Variant chr8-144416618-C-T is described in ClinVar as Benign. ClinVar VariationId is 362265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A4	NM_130849.4 link	c.172G>A	p.Ala58Thr	missense_variant	Exon 1 of 12	ENST00000301305.8	NP_570901.3	Q6P5W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC39A4	ENST00000301305.8 link	c.172G>A	p.Ala58Thr	missense_variant	Exon 1 of 12	1	NM_130849.4	ENSP00000301305.4	Q6P5W5-1
SLC39A4	ENST00000526658.1 link	c.172G>A	p.Ala58Thr	missense_variant	Exon 1 of 4	3		ENSP00000434512.1	E9PQ16
SLC39A4	ENST00000276833.9 link	c.-410G>A		upstream_gene_variant		2		ENSP00000276833.5	Q6P5W5-2

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78006

AN:

151892

Hom.:

20468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.507

GnomAD2 exomes

AF:

0.506

AC:

108910

AN:

215186

AF XY:

0.513

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.634

Gnomad EAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.556

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.547

AC:

789600

AN:

1442334

Hom.:

218714

Cov.:

AF XY:

0.547

AC XY:

391398

AN XY:

716030

show subpopulations

African (AFR)

AF:

0.438

AC:

14556

AN:

33236

American (AMR)

AF:

0.407

AC:

16885

AN:

41438

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

16227

AN:

25680

East Asian (EAS)

AF:

0.388

AC:

15078

AN:

38910

South Asian (SAS)

AF:

0.468

AC:

39274

AN:

83910

European-Finnish (FIN)

AF:

0.554

AC:

27852

AN:

50234

Middle Eastern (MID)

AF:

0.644

AC:

3564

AN:

5530

European-Non Finnish (NFE)

AF:

0.565

AC:

623732

AN:

1103782

Other (OTH)

AF:

0.544

AC:

32432

AN:

59614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

23579

47158

70736

94315

117894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17284

34568

51852

69136

86420

<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:

0.513

AC:

78037

AN:

152010

Hom.:

20470

Cov.:

AF XY:

0.511

AC XY:

38007

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.442

AC:

18305

AN:

41448

American (AMR)

AF:

0.458

AC:

7001

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

2206

AN:

3468

East Asian (EAS)

AF:

0.385

AC:

1990

AN:

5168

South Asian (SAS)

AF:

0.447

AC:

2160

AN:

4828

European-Finnish (FIN)

AF:

0.561

AC:

5935

AN:

10574

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.570

AC:

38732

AN:

67924

Other (OTH)

AF:

0.507

AC:

1067

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1989

3977

5966

7954

9943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.546

Hom.:

30080

Bravo

AF:

0.501

TwinsUK

AF:

0.563

AC:

2086

ALSPAC

AF:

0.548

AC:

2111

ESP6500AA

AF:

0.431

AC:

1886

ESP6500EA

AF:

0.570

AC:

4892

ExAC

AF:

0.484

AC:

57893

Asia WGS

AF:

0.414

AC:

1443

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary acrodermatitis enteropathica

Benign:3

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.024

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

0.0000064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

PhyloP100

-3.2

PrimateAI

Benign

0.47

PROVEAN

Benign

0.24

N;N

REVEL

Benign

0.077

Sift

Benign

0.98

T;T

Sift4G

Benign

0.54

T;.

Polyphen

0.0

B;.

Vest4

0.033

MPC

0.12

ClinPred

0.016

GERP RS

-9.4

PromoterAI

-0.067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.47

Mutation Taster

=99/1

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

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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