rs2293578

Variant names:

• chr11-47415852-C-T
• rs2293578
• NM_001128225.3:c.*489C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128225.3(SLC39A13):​c.*489C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 231,064 control chromosomes in the GnomAD database, including 10,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6500 hom., cov: 32)
  • Exomes 𝑓: 0.28 (3546 hom.)
• Consequence: SLC39A13 NM_001128225.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 33 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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Orphanet, G2P
• spondyloepimetaphyseal dysplasia-abnormal dentition syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

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.*489C>T		3_prime_UTR	Exon 10 of 10	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001441271.1		c.*489C>T		3_prime_UTR	Exon 11 of 11	NP_001428200.1
	SLC39A13	NM_152264.5		c.*489C>T		3_prime_UTR	Exon 10 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.*489C>T		3_prime_UTR	Exon 10 of 10	ENSP00000354689.4	Q96H72-1
	SLC39A13	ENST00000354884.8	TSL:1	c.*489C>T		3_prime_UTR	Exon 10 of 10	ENSP00000346956.4	Q96H72-2
	SLC39A13	ENST00000968896.1		c.*489C>T		3_prime_UTR	Exon 11 of 11	ENSP00000638955.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43155 AN: 152008 Hom.: 6486 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.283 AC: 22303 AN: 78938 Hom.: 3546 Cov.: 0 AF XY: 0.283 AC XY: 11976 AN XY: 42324

African (AFR) AF: 0.139 AC: 383 AN: 2758

American (AMR) AF: 0.364 AC: 1544 AN: 4240

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 466 AN: 1706

East Asian (EAS) AF: 0.262 AC: 1003 AN: 3834

South Asian (SAS) AF: 0.245 AC: 3067 AN: 12526

European-Finnish (FIN) AF: 0.279 AC: 887 AN: 3174

Middle Eastern (MID) AF: 0.325 AC: 98 AN: 302

European-Non Finnish (NFE) AF: 0.295 AC: 13730 AN: 46584

Other (OTH) AF: 0.295 AC: 1125 AN: 3814

GnomAD4 genome AF: 0.284 AC: 43191 AN: 152126 Hom.: 6500 Cov.: 32 AF XY: 0.285 AC XY: 21204 AN XY: 74368

African (AFR) AF: 0.169 AC: 7034 AN: 41504

American (AMR) AF: 0.372 AC: 5693 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1502 AN: 5162

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4822

European-Finnish (FIN) AF: 0.303 AC: 3211 AN: 10580

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22036 AN: 67986

Other (OTH) AF: 0.314 AC: 664 AN: 2112

Alfa AF: 0.308 Hom.: 1696

Bravo AF: 0.285

Asia WGS AF: 0.298 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2293578;

hg19: chr11-47437403;

COSMIC: COSV54080149;

COSMIC: COSV54080149;