17-72947776-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139177.4(SLC39A11):c.406G>A(p.Glu136Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A11 NM_139177.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85

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]

ACMG classification

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=0.22529775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A11	NM_139177.4	c.406G>A	p.Glu136Lys	missense_variant	5/10	ENST00000255559.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A11	ENST00000255559.8	c.406G>A	p.Glu136Lys	missense_variant	5/10	1	NM_139177.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.406G>A (p.E136K) alteration is located in exon 5 (coding exon 4) of the SLC39A11 gene. This alteration results from a G to A substitution at nucleotide position 406, causing the glutamic acid (E) at amino acid position 136 to be replaced by a lysine (K). 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	0.087
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	20
Dann	Uncertain	0.99
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.5	L;L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.7	N;N;.;.;.;.
REVEL	Benign	0.22
Sift	Benign	0.45	T;T;.;.;.;.
Sift4G	Benign	0.72	T;T;.;T;.;.
Polyphen		0.0040	B;B;.;.;.;.
Vest4		0.47
MutPred		0.49		Gain of ubiquitination at E136 (P = 0.0075);Gain of ubiquitination at E136 (P = 0.0075);.;Gain of ubiquitination at E136 (P = 0.0075);Gain of ubiquitination at E136 (P = 0.0075);Gain of ubiquitination at E136 (P = 0.0075);
MVP		0.61
MPC		0.16
ClinPred		0.55	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-70943915;