rs2293576

Variant names:

• chr11-47413435-G-A
• rs2293576
• NM_001128225.3:c.573G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-47413435-G-A
• chr11-47413435-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000362021.9(SLC39A13):​c.573G>A​(p.Ala191Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,866 control chromosomes in the GnomAD database, including 87,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5897 hom., cov: 33)
  • Exomes 𝑓: 0.33 (81548 hom.)
• Consequence: SLC39A13 ENST00000362021.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.557
• Publications: 57 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P, Orphanet, Genomics England PanelApp
• spondyloepimetaphyseal dysplasia-abnormal dentition syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-47413435-G-A is Benign according to our data. Variant chr11-47413435-G-A is described in ClinVar as Benign. ClinVar VariationId is 384707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.557 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000362021.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	NM_001128225.3	MANE Select	c.573G>A	p.Ala191Ala	synonymous	Exon 5 of 10	NP_001121697.2
	SLC39A13	NM_001441271.1		c.573G>A	p.Ala191Ala	synonymous	Exon 6 of 11	NP_001428200.1
	SLC39A13	NM_152264.5		c.573G>A	p.Ala191Ala	synonymous	Exon 5 of 10	NP_689477.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.573G>A	p.Ala191Ala	synonymous	Exon 5 of 10	ENSP00000354689.4
	SLC39A13	ENST00000354884.8	TSL:1	c.573G>A	p.Ala191Ala	synonymous	Exon 5 of 10	ENSP00000346956.4
	SLC39A13	ENST00000533076.5	TSL:2	c.573G>A	p.Ala191Ala	synonymous	Exon 5 of 11	ENSP00000434290.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37789 AN: 152046 Hom.: 5899 Cov.: 33

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.310 AC: 77694 AN: 250940 AF XY: 0.325

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.373

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.322

GnomAD4 exome AF: 0.327 AC: 478352 AN: 1461700 Hom.: 81548 Cov.: 57 AF XY: 0.332 AC XY: 241608 AN XY: 727170

African (AFR) AF: 0.0529 AC: 1772 AN: 33476

American (AMR) AF: 0.197 AC: 8806 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 9143 AN: 26126

East Asian (EAS) AF: 0.308 AC: 12222 AN: 39692

South Asian (SAS) AF: 0.451 AC: 38874 AN: 86246

European-Finnish (FIN) AF: 0.270 AC: 14435 AN: 53404

Middle Eastern (MID) AF: 0.306 AC: 1763 AN: 5764

European-Non Finnish (NFE) AF: 0.334 AC: 371700 AN: 1111898

Other (OTH) AF: 0.325 AC: 19637 AN: 60380

GnomAD4 genome AF: 0.248 AC: 37780 AN: 152166 Hom.: 5897 Cov.: 33 AF XY: 0.248 AC XY: 18424 AN XY: 74376

African (AFR) AF: 0.0617 AC: 2561 AN: 41528

American (AMR) AF: 0.231 AC: 3528 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5164

South Asian (SAS) AF: 0.452 AC: 2181 AN: 4826

European-Finnish (FIN) AF: 0.262 AC: 2776 AN: 10592

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22682 AN: 67966

Other (OTH) AF: 0.288 AC: 610 AN: 2116

Alfa AF: 0.315 Hom.: 15735

Bravo AF: 0.234

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Ehlers-Danlos syndrome, spondylocheirodysplastic type (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.4
DANN	Benign	0.85
PhyloP100		0.56
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

Other links and lift over

dbSNP: rs2293576; hg19: chr11-47434986; COSMIC: COSV61521013; COSMIC: COSV61521013;