chr17-72849683-C-G

Variant names:

• chr17-72849683-C-G
• rs1027614641
• NM_139177.4:c.552G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.43
• 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 4 ACMG points.

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

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.552G>C	p.Trp184Cys	missense	Exon 6 of 10	NP_631916.2	Q8N1S5-2
	SLC39A11	NM_001159770.2		c.573G>C	p.Trp191Cys	missense	Exon 6 of 10	NP_001153242.1	Q8N1S5-1
	SLC39A11	NM_001352692.2		c.573G>C	p.Trp191Cys	missense	Exon 6 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.552G>C	p.Trp184Cys	missense	Exon 6 of 10	ENSP00000255559.3	Q8N1S5-2
	SLC39A11	ENST00000952469.1		c.552G>C	p.Trp184Cys	missense	Exon 6 of 11	ENSP00000622528.1
	SLC39A11	ENST00000542342.6	TSL:2	c.573G>C	p.Trp191Cys	missense	Exon 6 of 10	ENSP00000445829.2	Q8N1S5-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 31

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

African (AFR) AF: 0.00 AC: 0 AN: 33078

American (AMR) AF: 0.00 AC: 0 AN: 43442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 85298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1109634

Other (OTH) AF: 0.00 AC: 0 AN: 60110

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	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
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
MetaSVM	Uncertain	0.46	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		6.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-11	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	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
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.95
gMVP		0.93
Mutation Taster		=10/90	disease causing

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

Other links and lift over

dbSNP: rs1027614641; hg19: chr17-70845822; COSMIC: COSV108081897; COSMIC: COSV108081897;