Variant 17-72649213-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_139177.4(SLC39A11):c.727C>A(p.Leu243Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,614,124 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 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SLC39A11
NM_139177.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

SLC39A11 (HGNC:14463): (solute carrier family 39 member 11) Predicted to enable zinc ion transmembrane transporter activity. Predicted to be involved in zinc ion transmembrane transport. Predicted to be located in Golgi apparatus; nucleus; and plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC39A11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34766954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A11	NM_139177.4 linkuse as main transcript	c.727C>A	p.Leu243Ile	missense_variant	8/10	ENST00000255559.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A11	ENST00000255559.8 linkuse as main transcript	c.727C>A	p.Leu243Ile	missense_variant	8/10	1	NM_139177.4	P4	Q8N1S5-2
SLC39A11	ENST00000542342.6 linkuse as main transcript	c.748C>A	p.Leu250Ile	missense_variant	8/10	2		A1	Q8N1S5-1
SLC39A11	ENST00000582769.5 linkuse as main transcript	c.475C>A	p.Leu159Ile	missense_variant	5/6	5
SLC39A11	ENST00000579988.1 linkuse as main transcript	n.154C>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152274

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:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000836

AC:

AN:

251162

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000142

AC:

207

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000125

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74396

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:

0.000235

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000818

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

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

Aug 02, 2021

The c.748C>A (p.L250I) alteration is located in exon 8 (coding exon 7) of the SLC39A11 gene. This alteration results from a C to A substitution at nucleotide position 748, causing the leucine (L) at amino acid position 250 to be replaced by an isoleucine (I). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.21

Cadd

Uncertain

Dann

Benign

0.95

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.017

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.76

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.19

Sift

Uncertain

0.025

D;T;.

Sift4G

Benign

0.22

T;T;.

Polyphen

1.0

D;D;.

Vest4

0.67

MVP

0.68

MPC

0.62

ClinPred

0.20

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.62

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