rs35741412

Variant names:

• chr11-47410213-G-A
• rs35741412
• NM_001128225.3:c.119G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-47410213-G-A
• chr11-47410213-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001128225.3(SLC39A13):​c.119G>A​(p.Arg40Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,613,426 control chromosomes in the GnomAD database, including 370 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 32)
  • Exomes 𝑓: 0.020 (350 hom.)
• Consequence: SLC39A13 NM_001128225.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.50
• Publications: 9 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: G2P, Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• spondyloepimetaphyseal dysplasia-abnormal dentition syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004864067).
• BP6: Variant 11-47410213-G-A is Benign according to our data. Variant chr11-47410213-G-A is described in ClinVar as Benign. ClinVar VariationId is 289730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.012 (1824/152304) while in subpopulation NFE AF = 0.0203 (1379/68016). AF 95% confidence interval is 0.0194. There are 20 homozygotes in GnomAd4. There are 809 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 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.119G>A	p.Arg40Gln	missense	Exon 2 of 10	NP_001121697.2	Q96H72-1
	SLC39A13	NM_001441271.1		c.119G>A	p.Arg40Gln	missense	Exon 3 of 11	NP_001428200.1
	SLC39A13	NM_152264.5		c.119G>A	p.Arg40Gln	missense	Exon 2 of 10	NP_689477.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.119G>A	p.Arg40Gln	missense	Exon 2 of 10	ENSP00000354689.4	Q96H72-1
	SLC39A13	ENST00000354884.8	TSL:1	c.119G>A	p.Arg40Gln	missense	Exon 2 of 10	ENSP00000346956.4	Q96H72-2
	SLC39A13	ENST00000968896.1		c.119G>A	p.Arg40Gln	missense	Exon 2 of 11	ENSP00000638955.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1826 AN: 152186 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.0132 AC: 3312 AN: 250168 AF XY: 0.0131

Gnomad AFR exome AF: 0.00442

Gnomad AMR exome AF: 0.00596

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00856

Gnomad NFE exome AF: 0.0229

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0196 AC: 28693 AN: 1461122 Hom.: 350 Cov.: 73 AF XY: 0.0192 AC XY: 13948 AN XY: 726896

African (AFR) AF: 0.00356 AC: 119 AN: 33472

American (AMR) AF: 0.00597 AC: 267 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00946 AC: 247 AN: 26112

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00289 AC: 249 AN: 86240

European-Finnish (FIN) AF: 0.00932 AC: 496 AN: 53214

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0237 AC: 26374 AN: 1111556

Other (OTH) AF: 0.0154 AC: 930 AN: 60370

GnomAD4 genome AF: 0.0120 AC: 1824 AN: 152304 Hom.: 20 Cov.: 32 AF XY: 0.0109 AC XY: 809 AN XY: 74468

African (AFR) AF: 0.00337 AC: 140 AN: 41568

American (AMR) AF: 0.0112 AC: 171 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.00602 AC: 64 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1379 AN: 68016

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.0181 Hom.: 74

Bravo AF: 0.0124

TwinsUK AF: 0.0232 AC: 86

ALSPAC AF: 0.0210 AC: 81

ESP6500AA AF: 0.00341 AC: 15

ESP6500EA AF: 0.0249 AC: 214

ExAC AF: 0.0145 AC: 1763

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0205

EpiControl AF: 0.0188

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Connective tissue disorder (1)
-	-	1	Ehlers-Danlos syndrome (1)
-	-	1	Ehlers-Danlos syndrome, spondylocheirodysplastic type (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.10
Sift	Benign	0.23	T
Sift4G	Benign	0.57	T
Polyphen		0.019	B
Vest4		0.094
MPC		0.39
ClinPred		0.0060	T
GERP RS		2.9
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.043
gMVP		0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs35741412; hg19: chr11-47431764; COSMIC: COSV99054928; COSMIC: COSV99054928;