rs117535951

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.251C>T(p.Pro84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,579,106 control chromosomes in the GnomAD database, including 1,055 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 81 hom., cov: 34)

Exomes 𝑓: 0.034 ( 974 hom. )

Consequence

SLC39A4
NM_130849.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.756

Publications

11 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: Genomics England PanelApp, Ambry Genetics, Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen

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=0.0023266077).

BP6

Variant 8-144416033-G-A is Benign according to our data. Variant chr8-144416033-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 362263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC39A4	NM_130849.4	MANE Select	c.251C>T	p.Pro84Leu	missense	Exon 2 of 12	NP_570901.3	Q6P5W5-1
SLC39A4	NM_017767.3		c.176C>T	p.Pro59Leu	missense	Exon 1 of 11	NP_060237.3	Q6P5W5-2
SLC39A4	NM_001374839.1		c.192+565C>T		intron	N/A	NP_001361768.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC39A4	ENST00000301305.8	TSL:1 MANE Select	c.251C>T	p.Pro84Leu	missense	Exon 2 of 12	ENSP00000301305.4	Q6P5W5-1
SLC39A4	ENST00000276833.9	TSL:2	c.176C>T	p.Pro59Leu	missense	Exon 1 of 11	ENSP00000276833.5	Q6P5W5-2
SLC39A4	ENST00000526658.1	TSL:3	c.192+565C>T		intron	N/A	ENSP00000434512.1	E9PQ16

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4148

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00686

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.0643

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0369

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0289

AC:

5805

AN:

200566

AF XY:

0.0297

show subpopulations

Gnomad AFR exome

AF:

0.00483

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0571

Gnomad EAS exome

AF:

0.0000639

Gnomad FIN exome

AF:

0.0678

Gnomad NFE exome

AF:

0.0383

Gnomad OTH exome

AF:

0.0336

GnomAD4 exome

AF:

0.0343

AC:

48890

AN:

1426892

Hom.:

974

Cov.:

AF XY:

0.0338

AC XY:

23893

AN XY:

705994

show subpopulations

African (AFR)

AF:

0.00617

AC:

204

AN:

33088

American (AMR)

AF:

0.0183

AC:

753

AN:

41048

Ashkenazi Jewish (ASJ)

AF:

0.0577

AC:

1465

AN:

25394

East Asian (EAS)

AF:

0.0000518

AC:

AN:

38642

South Asian (SAS)

AF:

0.00951

AC:

790

AN:

83062

European-Finnish (FIN)

AF:

0.0634

AC:

2833

AN:

44718

Middle Eastern (MID)

AF:

0.0595

AC:

339

AN:

5700

European-Non Finnish (NFE)

AF:

0.0367

AC:

40261

AN:

1096204

Other (OTH)

AF:

0.0380

AC:

2243

AN:

59036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3102

6203

9305

12406

15508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1522

3044

4566

6088

7610

<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:

0.0273

AC:

4148

AN:

152214

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2087

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00684

AC:

284

AN:

41532

American (AMR)

AF:

0.0209

AC:

320

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

210

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.00828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0643

AC:

683

AN:

10622

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0369

AC:

2507

AN:

67962

Other (OTH)

AF:

0.0303

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

220

441

661

882

1102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0359

Hom.:

Bravo

AF:

0.0236

TwinsUK

AF:

0.0235

AC:

ALSPAC

AF:

0.0394

AC:

152

ESP6500AA

AF:

0.00597

AC:

ESP6500EA

AF:

0.0353

AC:

301

ExAC

AF:

0.0254

AC:

3026

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary acrodermatitis enteropathica (4)

not provided (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.038

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-0.76

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.025

Sift

Uncertain

0.019

Sift4G

Uncertain

0.019

Polyphen

0.65

Vest4

0.068

MPC

0.13

ClinPred

0.0015

GERP RS

-1.1

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.032

gMVP

0.35

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

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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

Computational scores

Splicing

Publications

Other links and lift over