Variant 12-56232789-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173596.3(SLC39A5):c.388C>T(p.Arg130Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0014 in 1,612,570 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R130H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0074 ( 19 hom., cov: 30)

Exomes 𝑓: 0.00078 ( 19 hom. )

Consequence

SLC39A5
NM_173596.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.03

Variant links:

Genes affected

SLC39A5 (HGNC:20502): (solute carrier family 39 member 5) The protein encoded by this gene belongs to the ZIP family of zinc transporters that transport zinc into cells from outside, and play a crucial role in controlling intracellular zinc levels. Zinc is an essential cofactor for many enzymes and proteins involved in gene transcription, growth, development and differentiation. Mutations in this gene have been associated with autosomal dominant high myopia (MYP24). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

SLC39A5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049285293).

BP6

Variant 12-56232789-C-T is Benign according to our data. Variant chr12-56232789-C-T is described in ClinVar as [Benign]. Clinvar id is 785411.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00741 (1129/152280) while in subpopulation AFR AF= 0.0257 (1068/41560). AF 95% confidence interval is 0.0244. There are 19 homozygotes in gnomad4. There are 542 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A5	NM_173596.3 linkuse as main transcript	c.388C>T	p.Arg130Cys	missense_variant	5/13	ENST00000454355.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A5	ENST00000454355.7 linkuse as main transcript	c.388C>T	p.Arg130Cys	missense_variant	5/13	1	NM_173596.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00741

AC:

1127

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00196

AC:

488

AN:

249112

Hom.:

AF XY:

0.00144

AC XY:

194

AN XY:

134876

show subpopulations

Gnomad AFR exome

AF:

0.0276

Gnomad AMR exome

AF:

0.000973

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000987

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000777

AC:

1134

AN:

1460290

Hom.:

Cov.:

AF XY:

0.000626

AC XY:

455

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00741

AC:

1129

AN:

152280

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.000329

Hom.:

Bravo

AF:

0.00833

ESP6500AA

AF:

0.0263

AC:

116

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00249

AC:

302

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;T;T;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

T;.;T;T

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.0

D;N;D;N

REVEL

Benign

0.17

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.028

D;D;D;D

Polyphen

0.95

.;P;.;P

Vest4

0.22, 0.22

MVP

0.21

MPC

0.48

ClinPred

0.065

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over