dbSNP rs2234632: SLC39A2:p.Leu43Gln (chr14-20999754-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_014579.4(SLC39A2):c.128T>A(p.Leu43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,613,950 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L43R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0085 ( 19 hom., cov: 31)

Exomes 𝑓: 0.00088 ( 21 hom. )

Consequence

SLC39A2
NM_014579.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.419

Publications

31 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004229337).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00847 (1289/152124) while in subpopulation AFR AF = 0.0287 (1189/41498). AF 95% confidence interval is 0.0273. There are 19 homozygotes in GnomAd4. There are 592 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A2	NM_014579.4 link	c.128T>A	p.Leu43Gln	missense_variant	Exon 2 of 4	ENST00000298681.5	NP_055394.2	Q9NP94-1
SLC39A2	NM_001256588.2 link	c.128T>A	p.Leu43Gln	missense_variant	Exon 2 of 4		NP_001243517.1	Q9NP94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC39A2	ENST00000298681.5 link	c.128T>A	p.Leu43Gln	missense_variant	Exon 2 of 4	1	NM_014579.4	ENSP00000298681.4	Q9NP94-1
SLC39A2	ENST00000554422.5 link	c.128T>A	p.Leu43Gln	missense_variant	Exon 2 of 4	1		ENSP00000452568.1	Q9NP94-2
SLC39A2	ENST00000554128.1 link	n.284T>A		non_coding_transcript_exon_variant	Exon 2 of 2	4
ENSG00000258471	ENST00000647921.1 link	n.474A>T		non_coding_transcript_exon_variant	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.00848

AC:

1289

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00210

AC:

527

AN:

251294

AF XY:

0.00151

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000881

AC:

1288

AN:

1461826

Hom.:

Cov.:

AF XY:

0.000762

AC XY:

554

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0302

AC:

1010

AN:

33480

American (AMR)

AF:

0.00165

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1111960

Other (OTH)

AF:

0.00190

AC:

115

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

161

242

322

403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00847

AC:

1289

AN:

152124

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

592

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0287

AC:

1189

AN:

41498

American (AMR)

AF:

0.00438

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68008

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0000406

Hom.:

55285

ExAC

AF:

0.00278

AC:

337

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.4

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.053

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

PhyloP100

0.42

PrimateAI

Benign

0.25

PROVEAN

Benign

0.86

N;N

REVEL

Benign

0.046

Sift

Benign

0.14

T;T

Sift4G

Benign

0.091

T;T

Polyphen

0.0

.;B

Vest4

0.17

MVP

0.35

MPC

0.035

ClinPred

0.0078

GERP RS

2.8

PromoterAI

0.0033

Neutral

(source)

Varity_R

0.15

gMVP

0.36

Mutation Taster

=99/1

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over