Variant chr12-56231366-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173596.3(SLC39A5):c.92C>A(p.Pro31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

SLC39A5
NM_173596.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20375016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A5	NM_173596.3 linkuse as main transcript	c.92C>A	p.Pro31His	missense_variant	4/13	ENST00000454355.7	NP_775867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A5	ENST00000454355.7 linkuse as main transcript	c.92C>A	p.Pro31His	missense_variant	4/13	1	NM_173596.3	ENSP00000405360	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The c.92C>A (p.P31H) alteration is located in exon 4 (coding exon 1) of the SLC39A5 gene. This alteration results from a C to A substitution at nucleotide position 92, causing the proline (P) at amino acid position 31 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

.;T;T;.;T;.

Eigen

Benign

0.082

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.66

T;T;.;T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;.;M;.;M;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.6

D;D;N;D;N;D

REVEL

Benign

0.033

Sift

Uncertain

0.0010

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;T;D;T;D

Polyphen

0.68

.;.;P;.;P;.

Vest4

0.48, 0.47

MutPred

0.18

Gain of catalytic residue at P31 (P = 0.0914);Gain of catalytic residue at P31 (P = 0.0914);Gain of catalytic residue at P31 (P = 0.0914);Gain of catalytic residue at P31 (P = 0.0914);Gain of catalytic residue at P31 (P = 0.0914);Gain of catalytic residue at P31 (P = 0.0914);

MVP

0.21

MPC

0.56

ClinPred

0.97

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.32

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