Genetic Variant SLC39A2:p.Leu48Pro (chr14-20999769-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014579.4(SLC39A2):c.143T>C(p.Leu48Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0125 in 1,614,140 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 47 hom., cov: 33)

Exomes 𝑓: 0.012 ( 216 hom. )

Consequence

SLC39A2
NM_014579.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54

Publications

9 publications found

Variant links:

Genes affected

SLC39A2 (HGNC:17127): (solute carrier family 39 member 2) This gene encodes a member of the ZIP family of metal ion transporters. The encoded protein functions as a zinc transporter. Mutations in this gene may be associated with susceptibility to carotid artery disease. Multiple transcript variants have been described. [provided by RefSeq, Mar 2010]

SLC39A2 links:

ENSG00000258471 (HGNC:):

ENSG00000258471 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063932836).

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A2	NM_014579.4	MANE Select	c.143T>C	p.Leu48Pro	missense	Exon 2 of 4	NP_055394.2
	SLC39A2	NM_001256588.2		c.143T>C	p.Leu48Pro	missense	Exon 2 of 4	NP_001243517.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC39A2	ENST00000298681.5	TSL:1 MANE Select	c.143T>C	p.Leu48Pro	missense	Exon 2 of 4	ENSP00000298681.4
SLC39A2	ENST00000554422.5	TSL:1	c.143T>C	p.Leu48Pro	missense	Exon 2 of 4	ENSP00000452568.1
SLC39A2	ENST00000554128.1	TSL:4	n.299T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1912

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0825

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.0153

AC:

3841

AN:

251344

AF XY:

0.0149

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.0158

Gnomad ASJ exome

AF:

0.00446

Gnomad EAS exome

AF:

0.000652

Gnomad FIN exome

AF:

0.0743

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0125

AC:

18229

AN:

1461794

Hom.:

216

Cov.:

AF XY:

0.0123

AC XY:

8931

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

33480

American (AMR)

AF:

0.0142

AC:

635

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00402

AC:

105

AN:

26136

East Asian (EAS)

AF:

0.000605

AC:

AN:

39700

South Asian (SAS)

AF:

0.00194

AC:

167

AN:

86256

European-Finnish (FIN)

AF:

0.0690

AC:

3682

AN:

53392

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0117

AC:

12982

AN:

1111952

Other (OTH)

AF:

0.00970

AC:

586

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

940

1880

2820

3760

4700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.0126

AC:

1912

AN:

152346

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1193

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41584

American (AMR)

AF:

0.00764

AC:

117

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00186

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0825

AC:

876

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

785

AN:

68026

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

184

276

368

460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0107

Hom.:

Bravo

AF:

0.00761

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0112

AC:

ExAC

AF:

0.0146

AC:

1773

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.5

PhyloP100

5.5

PrimateAI

Uncertain

0.48

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.84

MPC

0.30

ClinPred

0.043

GERP RS

5.7

PromoterAI

0.027

Neutral

(source)

Varity_R

0.98

gMVP

0.85

Mutation Taster

=83/17

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

Computational scores

Splicing

Publications

Other links and lift over