NM_001128225.3:c.573G>A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001128225.3(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 NM_001128225.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.557

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 384707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47413435-G-A is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A13	NM_001128225.3	c.573G>A	p.Ala191Ala	synonymous_variant	Exon 5 of 10	ENST00000362021.9	NP_001121697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A13	ENST00000362021.9	c.573G>A	p.Ala191Ala	synonymous_variant	Exon 5 of 10	1	NM_001128225.3	ENSP00000354689.4

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

GnomAD3 exomes AF: 0.310 AC: 77694 AN: 250940 Hom.: 13532 AF XY: 0.325 AC XY: 44106 AN XY: 135754

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 SAS exome AF: 0.460

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

Gnomad4 AFR exome AF: 0.0529

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.325

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

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.288

Alfa AF: 0.317 Hom.: 13253

Bravo AF: 0.234

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Sep 30, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Ehlers-Danlos syndrome, spondylocheirodysplastic type Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

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