chr17-72649227-C-T

Variant names:

• chr17-72649227-C-T
• rs115567758
• NM_139177.4:c.713G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_139177.4(SLC39A11):​c.713G>A​(p.Gly238Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,844 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: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SLC39A11 NM_139177.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

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.713G>A	p.Gly238Asp	missense	Exon 8 of 10	NP_631916.2	Q8N1S5-2
	SLC39A11	NM_001159770.2		c.734G>A	p.Gly245Asp	missense	Exon 8 of 10	NP_001153242.1	Q8N1S5-1
	SLC39A11	NM_001352692.2		c.734G>A	p.Gly245Asp	missense	Exon 8 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.713G>A	p.Gly238Asp	missense	Exon 8 of 10	ENSP00000255559.3	Q8N1S5-2
	SLC39A11	ENST00000952469.1		c.878G>A	p.Gly293Asp	missense	Exon 9 of 11	ENSP00000622528.1
	SLC39A11	ENST00000542342.6	TSL:2	c.734G>A	p.Gly245Asp	missense	Exon 8 of 10	ENSP00000445829.2	Q8N1S5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	29
DANN	Benign	0.97
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Pathogenic	4.5	H
PhyloP100		7.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.94		Gain of relative solvent accessibility (P = 0.09)
MVP		0.79
MPC		0.71
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.99
gMVP		0.99
Mutation Taster		=3/97	disease causing

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

Other links and lift over

dbSNP: rs115567758; hg19: chr17-70645366;