11-47408665-G-T

Variant names:

• chr11-47408665-G-T
• rs920033870
• NM_001128225.3:c.-9+3G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001128225.3(SLC39A13):​c.-9+3G>T variant causes a splice 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. 2/3 splice prediction tools predicting alterations to normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.9756
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56
• Publications: 0 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]

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.-9+3G>T		splice_region intron	N/A	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001441271.1		c.-88+3G>T		splice_region intron	N/A	NP_001428200.1
	SLC39A13	NM_152264.5		c.-30+3G>T		splice_region intron	N/A	NP_689477.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.-9+3G>T		splice_region intron	N/A	ENSP00000354689.4	Q96H72-1
	SLC39A13	ENST00000354884.8	TSL:1	c.-30+3G>T		splice_region intron	N/A	ENSP00000346956.4	Q96H72-2
	SLC39A13	ENST00000968896.1		c.-9+3G>T		splice_region intron	N/A	ENSP00000638955.1

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

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.00 AC: 0 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14

East Asian (EAS) AF: 0.00 AC: 0 AN: 80

South Asian (SAS) AF: 0.00 AC: 0 AN: 714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1250

Other (OTH) AF: 0.00 AC: 0 AN: 48

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.95
PhyloP100		3.6
PromoterAI		-0.59	Under-expression
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

Other links and lift over

dbSNP: rs920033870; hg19: chr11-47430216;