11-47410089-C-T

Variant names:

• chr11-47410089-C-T
• rs370960489
• NM_001128225.3:c.-6C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001128225.3(SLC39A13):​c.-6C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000288 in 1,460,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: SLC39A13 NM_001128225.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.904
• 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]

SLC39A13 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, spondylocheirodysplastic type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia, ClinGen
• spondyloepimetaphyseal dysplasia-abnormal dentition syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

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.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001128225.3	MANE Select	c.-6C>T		splice_region	Exon 2 of 10	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001128225.3	MANE Select	c.-6C>T		5_prime_UTR	Exon 2 of 10	NP_001121697.2	Q96H72-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	ENSP00000354689.4	Q96H72-1
	SLC39A13	ENST00000354884.8	TSL:1	c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	ENSP00000346956.4	Q96H72-2
	SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.-6C>T		splice_region	Exon 2 of 10	ENSP00000354689.4	Q96H72-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000767 AC: 19 AN: 247594 AF XY: 0.0000668

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000818

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000900

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1460386 Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21 AN XY: 726500

African (AFR) AF: 0.0000598 AC: 2 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39698

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52424

Middle Eastern (MID) AF: 0.000185 AC: 1 AN: 5392

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 33

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000340

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	-0.29
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		0.90
PromoterAI		-0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs370960489; hg19: chr11-47431640; COSMIC: COSV100712696; COSMIC: COSV100712696;