17-72849683-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_139177.4(SLC39A11):​c.552G>C​(p.Trp184Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,608,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC39A11
NM_139177.4 missense

Scores

11
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.43
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC39A11NM_139177.4 linkc.552G>C p.Trp184Cys missense_variant Exon 6 of 10 ENST00000255559.8 NP_631916.2 Q8N1S5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC39A11ENST00000255559.8 linkc.552G>C p.Trp184Cys missense_variant Exon 6 of 10 1 NM_139177.4 ENSP00000255559.3 Q8N1S5-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152130
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1455922
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
724216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152130
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
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
Jun 09, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.573G>C (p.W191C) alteration is located in exon 6 (coding exon 5) of the SLC39A11 gene. This alteration results from a G to C substitution at nucleotide position 573, causing the tryptophan (W) at amino acid position 191 to be replaced by a cysteine (C). 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
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
31
DANN
Benign
0.95
DEOGEN2
Benign
0.24
.;T;.;T;T;T
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.90
D;D;D;D;D;D
MetaSVM
Uncertain
0.46
D
MutationAssessor
Pathogenic
2.9
.;M;.;.;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-11
D;D;.;.;.;.
REVEL
Pathogenic
0.82
Sift
Uncertain
0.0010
D;D;.;.;.;.
Sift4G
Pathogenic
0.0
D;D;.;D;D;.
Polyphen
1.0
D;D;.;.;.;.
Vest4
0.88
MutPred
0.62
.;Loss of MoRF binding (P = 0.0074);.;.;.;.;
MVP
0.82
MPC
0.79
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.95
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1027614641; hg19: chr17-70845822; API