chr11-47409959-C-T

Variant names:

• chr11-47409959-C-T
• rs140346957
• NM_001128225.3:c.-8-128C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001128225.3(SLC39A13):​c.-8-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,096,518 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (5 hom.)
• Consequence: SLC39A13 NM_001128225.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.712
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-47409959-C-T is Benign according to our data. Variant chr11-47409959-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1215474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.-8-128C>T		intron	N/A	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001441271.1		c.-8-128C>T		intron	N/A	NP_001428200.1
	SLC39A13	NM_152264.5		c.-29-107C>T		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.-8-128C>T		intron	N/A	ENSP00000354689.4	Q96H72-1
	SLC39A13	ENST00000354884.8	TSL:1	c.-29-107C>T		intron	N/A	ENSP00000346956.4	Q96H72-2
	SLC39A13	ENST00000869747.1		c.-32C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000539806.1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 464 AN: 152240 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000325 AC: 307 AN: 944160 Hom.: 5 Cov.: 12 AF XY: 0.000268 AC XY: 130 AN XY: 484718

African (AFR) AF: 0.0104 AC: 243 AN: 23264

American (AMR) AF: 0.000542 AC: 20 AN: 36928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19402

East Asian (EAS) AF: 0.0000807 AC: 3 AN: 37156

South Asian (SAS) AF: 0.0000296 AC: 2 AN: 67512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37784

Middle Eastern (MID) AF: 0.000663 AC: 2 AN: 3016

European-Non Finnish (NFE) AF: 0.0000222 AC: 15 AN: 675950

Other (OTH) AF: 0.000510 AC: 22 AN: 43148

GnomAD4 genome AF: 0.00303 AC: 462 AN: 152358 Hom.: 2 Cov.: 33 AF XY: 0.00283 AC XY: 211 AN XY: 74504

African (AFR) AF: 0.0105 AC: 436 AN: 41578

American (AMR) AF: 0.000719 AC: 11 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00312

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.81
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-0.71
PromoterAI		-0.032	Neutral
Mutation Taster		=100/0	polymorphism

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: rs140346957; hg19: chr11-47431510;