11-47410129-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128225.3(SLC39A13):​c.35C>G​(p.Ala12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A12V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SLC39A13
NM_001128225.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.813
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19679028).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC39A13NM_001128225.3 linkc.35C>G p.Ala12Gly missense_variant Exon 2 of 10 ENST00000362021.9 NP_001121697.2 Q96H72-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC39A13ENST00000362021.9 linkc.35C>G p.Ala12Gly missense_variant Exon 2 of 10 1 NM_001128225.3 ENSP00000354689.4 Q96H72-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460834
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726732
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.043
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
T;T;.;T;T;.;.;.;T
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.88
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.20
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
0.81
.;.;.;.;L;L;.;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.013
D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.038
D;D;D;D;T;T;D;D;D
Polyphen
1.0
.;.;.;.;D;D;.;.;D
Vest4
0.31
MutPred
0.18
Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP
0.64
MPC
0.35
ClinPred
0.63
D
GERP RS
2.4
Varity_R
0.092
gMVP
0.70

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47431680; API