chr8-144415944-C-T

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.340G>A(p.Ala114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,591,926 control chromosomes in the GnomAD database, including 195,443 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 0.44 ( 15453 hom., cov: 33)

Exomes 𝑓: 0.50 ( 179990 hom. )

Consequence

SLC39A4
NM_130849.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.383

Publications

29 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=1.969787E-5).

BP6

Variant 8-144415944-C-T is Benign according to our data. Variant chr8-144415944-C-T is described in ClinVar as Benign. ClinVar VariationId is 362260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 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.340G>A	p.Ala114Thr	missense	Exon 2 of 12	NP_570901.3	Q6P5W5-1
SLC39A4	NM_017767.3		c.265G>A	p.Ala89Thr	missense	Exon 1 of 11	NP_060237.3	Q6P5W5-2
SLC39A4	NM_001374839.1		c.193-525G>A		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.340G>A	p.Ala114Thr	missense	Exon 2 of 12	ENSP00000301305.4	Q6P5W5-1
SLC39A4	ENST00000276833.9	TSL:2	c.265G>A	p.Ala89Thr	missense	Exon 1 of 11	ENSP00000276833.5	Q6P5W5-2
SLC39A4	ENST00000526658.1	TSL:3	c.193-525G>A		intron	N/A	ENSP00000434512.1	E9PQ16

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66765

AN:

151934

Hom.:

15455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.458

AC:

97205

AN:

212328

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.595

Gnomad EAS exome

AF:

0.368

Gnomad FIN exome

AF:

0.517

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.485

GnomAD4 exome

AF:

0.496

AC:

714316

AN:

1439874

Hom.:

179990

Cov.:

AF XY:

0.494

AC XY:

353224

AN XY:

714592

show subpopulations

African (AFR)

AF:

0.297

AC:

9888

AN:

33334

American (AMR)

AF:

0.376

AC:

15666

AN:

41620

Ashkenazi Jewish (ASJ)

AF:

0.592

AC:

15198

AN:

25678

East Asian (EAS)

AF:

0.386

AC:

15054

AN:

39012

South Asian (SAS)

AF:

0.393

AC:

32949

AN:

83818

European-Finnish (FIN)

AF:

0.512

AC:

24245

AN:

47370

Middle Eastern (MID)

AF:

0.604

AC:

3454

AN:

5716

European-Non Finnish (NFE)

AF:

0.515

AC:

568236

AN:

1103750

Other (OTH)

AF:

0.497

AC:

29626

AN:

59576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

23323

46646

69969

93292

116615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16272

32544

48816

65088

81360

<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:

0.439

AC:

66786

AN:

152052

Hom.:

15453

Cov.:

AF XY:

0.438

AC XY:

32592

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.297

AC:

12328

AN:

41484

American (AMR)

AF:

0.410

AC:

6265

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.598

AC:

2076

AN:

3470

East Asian (EAS)

AF:

0.382

AC:

1970

AN:

5154

South Asian (SAS)

AF:

0.381

AC:

1834

AN:

4818

European-Finnish (FIN)

AF:

0.518

AC:

5492

AN:

10596

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35289

AN:

67920

Other (OTH)

AF:

0.447

AC:

944

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1904

3809

5713

7618

9522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.502

Hom.:

6264

Bravo

AF:

0.425

TwinsUK

AF:

0.512

AC:

1898

ALSPAC

AF:

0.503

AC:

1940

ESP6500AA

AF:

0.284

AC:

1238

ESP6500EA

AF:

0.512

AC:

4378

ExAC

AF:

0.433

AC:

51499

Asia WGS

AF:

0.385

AC:

1341

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary acrodermatitis enteropathica (3)

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.3

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.018

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.74

MetaRNN

Benign

0.000020

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PhyloP100

-0.38

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.17

REVEL

Benign

0.059

Sift

Benign

1.0

Sift4G

Benign

0.20

Polyphen

0.43

Vest4

0.047

MPC

0.20

ClinPred

0.0093

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.35

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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