17-72647616-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_139177.4(SLC39A11):​c.976G>C​(p.Val326Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SLC39A11
NM_139177.4 missense

Scores

2
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC39A11NM_139177.4 linkc.976G>C p.Val326Leu missense_variant Exon 10 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.976G>C p.Val326Leu missense_variant Exon 10 of 10 1 NM_139177.4 ENSP00000255559.3 Q8N1S5-2
SLC39A11ENST00000542342.6 linkc.997G>C p.Val333Leu missense_variant Exon 10 of 10 2 ENSP00000445829.2 Q8N1S5-1
SLC39A11ENST00000579988.1 linkn.403G>C non_coding_transcript_exon_variant Exon 4 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251260
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135842
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461762
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727182
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:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.997G>C (p.V333L) alteration is located in exon 10 (coding exon 9) of the SLC39A11 gene. This alteration results from a G to C substitution at nucleotide position 997, causing the valine (V) at amino acid position 333 to be replaced by a leucine (L). 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
Uncertain
0.032
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
.;T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.15
Sift
Benign
0.15
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.38
B;B
Vest4
0.63
MutPred
0.49
.;Gain of disorder (P = 0.2282);
MVP
0.42
MPC
0.34
ClinPred
0.87
D
GERP RS
5.4
Varity_R
0.31
gMVP
0.73

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.

Other links and lift over

dbSNP: rs776772108; hg19: chr17-70643755; API