Genetic Variant SLC39A2:p.Phe115Leu (chr14-21000992-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014579.4(SLC39A2):c.343T>C(p.Phe115Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,525,850 control chromosomes in the GnomAD database, including 97,895 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8451 hom., cov: 32)

Exomes 𝑓: 0.36 ( 89444 hom. )

Consequence

SLC39A2
NM_014579.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

23 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3463368E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A2	NM_014579.4 link	c.343T>C	p.Phe115Leu	missense_variant	Exon 4 of 4	ENST00000298681.5	NP_055394.2	Q9NP94-1
SLC39A2	NM_001256588.2 link	c.*80T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001243517.1	Q9NP94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC39A2	ENST00000298681.5 link	c.343T>C	p.Phe115Leu	missense_variant	Exon 4 of 4	1	NM_014579.4	ENSP00000298681.4	Q9NP94-1
SLC39A2	ENST00000554422.5 link	c.*80T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000452568.1	Q9NP94-2
ENSG00000258471	ENST00000647921.1 link	n.398-1162A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48303

AN:

151932

Hom.:

8447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.355

GnomAD2 exomes

AF:

0.367

AC:

69296

AN:

189048

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.357

AC:

490807

AN:

1373800

Hom.:

89444

Cov.:

AF XY:

0.357

AC XY:

240520

AN XY:

673836

show subpopulations

African (AFR)

AF:

0.163

AC:

4964

AN:

30474

American (AMR)

AF:

0.500

AC:

15841

AN:

31658

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

8289

AN:

20702

East Asian (EAS)

AF:

0.435

AC:

16911

AN:

38892

South Asian (SAS)

AF:

0.342

AC:

24129

AN:

70640

European-Finnish (FIN)

AF:

0.379

AC:

19067

AN:

50354

Middle Eastern (MID)

AF:

0.375

AC:

1901

AN:

5074

European-Non Finnish (NFE)

AF:

0.355

AC:

379532

AN:

1069548

Other (OTH)

AF:

0.357

AC:

20173

AN:

56458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

16640

33280

49919

66559

83199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.318

AC:

48326

AN:

152050

Hom.:

8451

Cov.:

AF XY:

0.324

AC XY:

24083

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.173

AC:

7183

AN:

41514

American (AMR)

AF:

0.455

AC:

6937

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1457

AN:

3468

East Asian (EAS)

AF:

0.383

AC:

1980

AN:

5164

South Asian (SAS)

AF:

0.342

AC:

1649

AN:

4816

European-Finnish (FIN)

AF:

0.360

AC:

3809

AN:

10566

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24137

AN:

67960

Other (OTH)

AF:

0.352

AC:

740

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1636

3272

4909

6545

8181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.343

Hom.:

42725

Bravo

AF:

0.318

TwinsUK

AF:

0.351

AC:

1300

ALSPAC

AF:

0.354

AC:

1365

ESP6500AA

AF:

0.184

AC:

810

ESP6500EA

AF:

0.352

AC:

3024

ExAC

AF:

0.353

AC:

42618

Asia WGS

AF:

0.328

AC:

1139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.078

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.026

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.47

MetaRNN

Benign

0.00023

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.97

PhyloP100

-1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

1.4

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.014

MutPred

0.58

Loss of catalytic residue at F115 (P = 0.269);

MPC

0.037

ClinPred

0.023

GERP RS

-11

Varity_R

0.086

gMVP

0.23

Mutation Taster

=86/14

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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14-21000992-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over