11-47408907-T-C

Variant names:

• chr11-47408907-T-C
• rs7937331
• NM_001128225.3:c.-9+245T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001128225.3(SLC39A13):​c.-9+245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,486 control chromosomes in the GnomAD database, including 31,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (31796 hom., cov: 31)
  • Exomes 𝑓: 0.65 (120 hom.)
• Consequence: SLC39A13 NM_001128225.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• Publications: 16 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-47408907-T-C is Benign according to our data. Variant chr11-47408907-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 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.-9+245T>C		intron	N/A	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001441271.1		c.-88+245T>C		intron	N/A	NP_001428200.1
	SLC39A13	NM_152264.5		c.-30+245T>C		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+245T>C		intron	N/A	ENSP00000354689.4	Q96H72-1
	SLC39A13	ENST00000354884.8	TSL:1	c.-30+245T>C		intron	N/A	ENSP00000346956.4	Q96H72-2
	SLC39A13	ENST00000968896.1		c.-9+245T>C		intron	N/A	ENSP00000638955.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98181 AN: 151794 Hom.: 31793 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.653 AC: 375 AN: 574 Hom.: 120 Cov.: 0 AF XY: 0.653 AC XY: 282 AN XY: 432

African (AFR) AF: 0.600 AC: 6 AN: 10

American (AMR) AF: 0.667 AC: 4 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.750 AC: 9 AN: 12

South Asian (SAS) AF: 0.625 AC: 10 AN: 16

European-Finnish (FIN) AF: 0.683 AC: 41 AN: 60

Middle Eastern (MID) AF: 0.500 AC: 4 AN: 8

European-Non Finnish (NFE) AF: 0.653 AC: 273 AN: 418

Other (OTH) AF: 0.636 AC: 28 AN: 44

GnomAD4 genome AF: 0.646 AC: 98208 AN: 151912 Hom.: 31796 Cov.: 31 AF XY: 0.647 AC XY: 48047 AN XY: 74242

African (AFR) AF: 0.607 AC: 25151 AN: 41432

American (AMR) AF: 0.606 AC: 9254 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2413 AN: 3470

East Asian (EAS) AF: 0.706 AC: 3622 AN: 5128

South Asian (SAS) AF: 0.696 AC: 3358 AN: 4822

European-Finnish (FIN) AF: 0.680 AC: 7176 AN: 10556

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45316 AN: 67912

Other (OTH) AF: 0.634 AC: 1338 AN: 2110

Alfa AF: 0.656 Hom.: 15640

Bravo AF: 0.639

Asia WGS AF: 0.681 AC: 2366 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.51
PhyloP100		-1.1
PromoterAI		0.035	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7937331; hg19: chr11-47430458;