rs148291843

Variant names:

• chr11-47412369-C-G
• rs148291843
• NM_001128225.3:c.439C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001128225.3(SLC39A13):​c.439C>G​(p.Gln147Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00265 in 1,614,098 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (8 hom.)
• Consequence: SLC39A13 NM_001128225.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:10
• Conservation: PhyloP100: 3.85
• Publications: 11 publications found

Genes affected

SLC39A13 (HGNC:20859): (solute carrier family 39 member 13) This gene encodes a member of the LIV-1 subfamily of the ZIP transporter family. The encoded transmembrane protein functions as a zinc transporter. Mutations in this gene have been associated with the spondylocheiro dysplastic form of Ehlers-Danlos syndrome. Alternate transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

SLC39A13 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, spondylocheirodysplastic type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia, ClinGen
• spondyloepimetaphyseal dysplasia-abnormal dentition syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009007037).
• BP6: Variant 11-47412369-C-G is Benign according to our data. Variant chr11-47412369-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 287155.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128225.3. 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
	SLC39A13	NM_001128225.3	MANE Select	c.439C>G	p.Gln147Glu	missense	Exon 4 of 10	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001441271.1		c.439C>G	p.Gln147Glu	missense	Exon 5 of 11	NP_001428200.1
	SLC39A13	NM_152264.5		c.439C>G	p.Gln147Glu	missense	Exon 4 of 10	NP_689477.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.439C>G	p.Gln147Glu	missense	Exon 4 of 10	ENSP00000354689.4	Q96H72-1
	SLC39A13	ENST00000354884.8	TSL:1	c.439C>G	p.Gln147Glu	missense	Exon 4 of 10	ENSP00000346956.4	Q96H72-2
	SLC39A13	ENST00000968896.1		c.439C>G	p.Gln147Glu	missense	Exon 4 of 11	ENSP00000638955.1

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 313 AN: 152242 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00170 AC: 425 AN: 250280 AF XY: 0.00179

Gnomad AFR exome AF: 0.000433

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00182

Gnomad NFE exome AF: 0.00281

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00271 AC: 3959 AN: 1461738 Hom.: 8 Cov.: 32 AF XY: 0.00267 AC XY: 1943 AN XY: 727168

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.000850 AC: 38 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00306 AC: 80 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86250

European-Finnish (FIN) AF: 0.00122 AC: 65 AN: 53378

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00324 AC: 3601 AN: 1111930

Other (OTH) AF: 0.00255 AC: 154 AN: 60384

GnomAD4 genome AF: 0.00205 AC: 313 AN: 152360 Hom.: 3 Cov.: 33 AF XY: 0.00203 AC XY: 151 AN XY: 74510

African (AFR) AF: 0.000481 AC: 20 AN: 41584

American (AMR) AF: 0.00379 AC: 58 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00298 AC: 203 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00270 Hom.: 1

Bravo AF: 0.00193

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00152 AC: 184

EpiCase AF: 0.00371

EpiControl AF: 0.00231

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Ehlers-Danlos syndrome, spondylocheirodysplastic type (2)
-	-	2	not specified (2)
-	-	1	Ehlers-Danlos syndrome (1)
-	1	-	Inborn genetic diseases (1)
-	-	1	SLC39A13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.51	N
PhyloP100		3.9
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.084	B
Vest4		0.41
MVP		0.39
MPC		0.46
ClinPred		0.022	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.29
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs148291843; hg19: chr11-47433920; COSMIC: COSV100712659; COSMIC: COSV100712659;