11-47408665-G-T

Position:

• chr11-47408665-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128225.3(SLC39A13):​c.-9+3G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC39A13 NM_001128225.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.9756
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56

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-AS1 (HGNC:56351): (SLC39A13 antisense RNA 1)

SPI1 (HGNC:11241): (Spi-1 proto-oncogene) This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear protein binds to a purine-rich sequence known as the PU-box found near the promoters of target genes, and regulates their expression in coordination with other transcription factors and cofactors. The protein can also regulate alternative splicing of target genes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A13	NM_001128225.3	c.-9+3G>T		splice_donor_region_variant, intron_variant		ENST00000362021.9
SLC39A13-AS1	NR_182305.1	n.331+287C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A13	ENST00000362021.9	c.-9+3G>T		splice_donor_region_variant, intron_variant		1	NM_001128225.3	P4
SLC39A13-AS1	ENST00000666926.1	n.320+287C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2144 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1452

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 30, 2017

The c.-30+3 G>T variant of uncertain significance in the SLC39A13 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is located in intron 1 of the 5' untranslated region of the SLC39A13 gene, which is the non-coding region upstream of the start codon located in exon 2. Specifically, this variant occurs in the natural splice donor site of intron 1, at a nucleotide that is conserved in mammals. However, in silico splice algorithms predict that this variant likely does not alter splicing. Additionally, no other regulatory or splice site variants in the SLC39A13 gene have been reported in HGMD in association with spEDS to date (Stenson et al., 2014). Nevertheless, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. Furthermore, data from control individuals was not available to assess whether c.-30+3 G>T may be a common benign variant in the general population.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.77
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

Publications

LitVar

Other links and lift over

dbSNP: rs920033870; hg19: chr11-47430216;