rs2010519

Variant names:

• chr11-47410177-A-C
• rs2010519
• NM_001128225.3:c.83A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-47410177-A-C
• chr11-47410177-A-G
• chr11-47410177-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001128225.3(SLC39A13):​c.83A>C​(p.Glu28Ala) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E28G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC39A13 NM_001128225.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 31 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P, Orphanet, Genomics England PanelApp
• spondyloepimetaphyseal dysplasia-abnormal dentition syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038045406).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	NM_001128225.3	MANE Select	c.83A>C	p.Glu28Ala	missense	Exon 2 of 10	NP_001121697.2
	SLC39A13	NM_001441271.1		c.83A>C	p.Glu28Ala	missense	Exon 3 of 11	NP_001428200.1
	SLC39A13	NM_152264.5		c.83A>C	p.Glu28Ala	missense	Exon 2 of 10	NP_689477.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A13	ENST00000362021.9	TSL:1 MANE Select	c.83A>C	p.Glu28Ala	missense	Exon 2 of 10	ENSP00000354689.4
	SLC39A13	ENST00000354884.8	TSL:1	c.83A>C	p.Glu28Ala	missense	Exon 2 of 10	ENSP00000346956.4
	SLC39A13	ENST00000533076.5	TSL:2	c.83A>C	p.Glu28Ala	missense	Exon 2 of 11	ENSP00000434290.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.45
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.10
Sift	Benign	0.23	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.11
MutPred		0.12		Gain of methylation at R29 (P = 0.0694)
MVP		0.37
MPC		0.36
ClinPred		0.083	T
GERP RS		4.2
PromoterAI		0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.047
gMVP		0.67
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: rs2010519; hg19: chr11-47431728;