17-72947776-C-G

Variant names:

• chr17-72947776-C-G
• rs2085524968
• NM_139177.4:c.406G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139177.4(SLC39A11):​c.406G>C​(p.Glu136Gln) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E136K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC39A11 NM_139177.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21743193).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139177.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A11	NM_139177.4	MANE Select	c.406G>C	p.Glu136Gln	missense	Exon 5 of 10	NP_631916.2	Q8N1S5-2
	SLC39A11	NM_001159770.2		c.406G>C	p.Glu136Gln	missense	Exon 5 of 10	NP_001153242.1	Q8N1S5-1
	SLC39A11	NM_001352692.2		c.406G>C	p.Glu136Gln	missense	Exon 5 of 10	NP_001339621.1	Q8N1S5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A11	ENST00000255559.8	TSL:1 MANE Select	c.406G>C	p.Glu136Gln	missense	Exon 5 of 10	ENSP00000255559.3	Q8N1S5-2
	SLC39A11	ENST00000952469.1		c.406G>C	p.Glu136Gln	missense	Exon 5 of 11	ENSP00000622528.1
	SLC39A11	ENST00000542342.6	TSL:2	c.406G>C	p.Glu136Gln	missense	Exon 5 of 10	ENSP00000445829.2	Q8N1S5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.099
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.054
Sift	Benign	0.27	T
Sift4G	Benign	0.49	T
Polyphen		0.21	B
Vest4		0.42
MutPred		0.40		Loss of phosphorylation at S137 (P = 0.1012)
MVP		0.62
MPC		0.19
ClinPred		0.55	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2085524968; hg19: chr17-70943915;