Variant 12-56234869-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173596.3(SLC39A5):c.517G>A(p.Ala173Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000336 in 1,613,658 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 3 hom. )

Consequence

SLC39A5
NM_173596.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.58

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064778626).

BP6

Variant 12-56234869-G-A is Benign according to our data. Variant chr12-56234869-G-A is described in ClinVar as [Benign]. Clinvar id is 778446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A5	NM_173596.3 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	6/13	ENST00000454355.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC39A5	ENST00000454355.7 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	6/13	1	NM_173596.3	P1
SLC39A5	ENST00000266980.8 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	4/11	1		P1
SLC39A5	ENST00000436633.5 linkuse as main transcript	c.430G>A	p.Ala144Thr	missense_variant	6/7	5
SLC39A5	ENST00000481103.5 linkuse as main transcript	n.386G>A		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00120

AC:

300

AN:

250676

Hom.:

AF XY:

0.000862

AC XY:

117

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.00755

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000329

AC:

481

AN:

1461370

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

208

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00722

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000401

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.000793

ExAC

AF:

0.00110

AC:

134

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0058

T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

MetaRNN

Benign

0.0065

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

L;.;L

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.35

N;N;N

REVEL

Benign

0.089

Sift

Benign

0.41

T;D;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.87

P;.;P

Vest4

0.36

MVP

0.63

MPC

0.36

ClinPred

0.037

GERP RS

4.6

Varity_R

0.11

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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