rs35690712

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006979.3(SLC39A7):c.370G>C(p.Gly124Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 1,612,224 control chromosomes in the GnomAD database, including 1,244 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. G124G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.029 ( 120 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1124 hom. )

Consequence

SLC39A7
NM_006979.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.806

Publications

15 publications found

Variant links:

Genes affected

SLC39A7 (HGNC:4927): (solute carrier family 39 member 7) The protein encoded by this gene transports zinc from the Golgi and endoplasmic reticulum to the cytoplasm. This transport may be important for activation of tyrosine kinases, some of which could be involved in cancer progression. Therefore, modulation of the encoded protein could be useful as a therapeutic agent against cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

SLC39A7 Gene-Disease associations (from GenCC):

agammaglobulinemia 9, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
agammaglobulinemia
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

SLC39A7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016112626).

BP6

Variant 6-33201615-G-C is Benign according to our data. Variant chr6-33201615-G-C is described in ClinVar as Benign. ClinVar VariationId is 1167251.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A7	NM_006979.3 link	c.370G>C	p.Gly124Arg	missense_variant	Exon 1 of 7	ENST00000374677.8	NP_008910.2	Q92504A0A024RCX7
SLC39A7	NM_001077516.2 link	c.370G>C	p.Gly124Arg	missense_variant	Exon 2 of 8		NP_001070984.1	Q92504A0A024RCX7
SLC39A7	NM_001288777.2 link	c.53-146G>C		intron_variant	Intron 2 of 7		NP_001275706.1	Q92504B4DZZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A7	ENST00000374677.8 link	c.370G>C	p.Gly124Arg	missense_variant	Exon 1 of 7	1	NM_006979.3	ENSP00000363809.3		Q92504

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4438

AN:

152126

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00859

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.00676

Gnomad SAS

AF:

0.0512

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0373

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0354

AC:

8828

AN:

249126

AF XY:

0.0376

show subpopulations

Gnomad AFR exome

AF:

0.00807

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.00873

Gnomad FIN exome

AF:

0.0232

Gnomad NFE exome

AF:

0.0371

Gnomad OTH exome

AF:

0.0457

GnomAD4 exome

AF:

0.0334

AC:

48729

AN:

1459980

Hom.:

1124

Cov.:

AF XY:

0.0348

AC XY:

25260

AN XY:

725938

show subpopulations

African (AFR)

AF:

0.0111

AC:

371

AN:

33452

American (AMR)

AF:

0.0192

AC:

857

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3313

AN:

26118

East Asian (EAS)

AF:

0.00439

AC:

174

AN:

39642

South Asian (SAS)

AF:

0.0513

AC:

4426

AN:

86230

European-Finnish (FIN)

AF:

0.0234

AC:

1242

AN:

53158

Middle Eastern (MID)

AF:

0.0719

AC:

415

AN:

5768

European-Non Finnish (NFE)

AF:

0.0321

AC:

35657

AN:

1110638

Other (OTH)

AF:

0.0377

AC:

2274

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2663

5326

7989

10652

13315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1256

2512

3768

5024

6280

<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:

0.0291

AC:

4436

AN:

152244

Hom.:

120

Cov.:

AF XY:

0.0284

AC XY:

2113

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00864

AC:

359

AN:

41558

American (AMR)

AF:

0.0284

AC:

435

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

480

AN:

3472

East Asian (EAS)

AF:

0.00678

AC:

AN:

5166

South Asian (SAS)

AF:

0.0510

AC:

246

AN:

4820

European-Finnish (FIN)

AF:

0.0221

AC:

234

AN:

10612

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0373

AC:

2537

AN:

67992

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

211

422

633

844

1055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0416

Hom.:

156

Bravo

AF:

0.0276

TwinsUK

AF:

0.0318

AC:

118

ALSPAC

AF:

0.0296

AC:

114

ESP6500AA

AF:

0.00689

AC:

ESP6500EA

AF:

0.0391

AC:

328

ExAC

AF:

0.0354

AC:

4277

Asia WGS

AF:

0.0320

AC:

115

AN:

3478

EpiCase

AF:

0.0415

EpiControl

AF:

0.0433

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.082

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PhyloP100

0.81

PrimateAI

Benign

0.46

PROVEAN

Benign

0.56

N;N

REVEL

Benign

0.041

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.64

T;T

Polyphen

0.0

B;B

Vest4

0.12

MPC

1.0

ClinPred

0.0054

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.44

Mutation Taster

=91/9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over