rs200490683
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001128225.3(SLC39A13):c.635G>A(p.Arg212Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,614,046 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R212W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001128225.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC39A13 | NM_001128225.3 | c.635G>A | p.Arg212Gln | missense_variant | 5/10 | ENST00000362021.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC39A13 | ENST00000362021.9 | c.635G>A | p.Arg212Gln | missense_variant | 5/10 | 1 | NM_001128225.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000164 AC: 41AN: 250378Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135572
GnomAD4 exome AF: 0.000172 AC: 252AN: 1461714Hom.: 1 Cov.: 34 AF XY: 0.000173 AC XY: 126AN XY: 727172
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74494
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 25, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 23, 2020 | - - |
Ehlers-Danlos syndrome, spondylocheirodysplastic type Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 08, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 212 of the SLC39A13 protein (p.Arg212Gln). This variant is present in population databases (rs200490683, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SLC39A13-related conditions. ClinVar contains an entry for this variant (Variation ID: 469535). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 01, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.635G>A (p.R212Q) alteration is located in exon 5 (coding exon 4) of the SLC39A13 gene. This alteration results from a G to A substitution at nucleotide position 635, causing the arginine (R) at amino acid position 212 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at