rs767784704
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001128225.3(SLC39A13):c.736A>G(p.Ile246Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000186 in 1,609,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I246I) has been classified as Likely benign.
Frequency
Consequence
NM_001128225.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC39A13 | NM_001128225.3 | c.736A>G | p.Ile246Val | missense_variant, splice_region_variant | 7/10 | ENST00000362021.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC39A13 | ENST00000362021.9 | c.736A>G | p.Ile246Val | missense_variant, splice_region_variant | 7/10 | 1 | NM_001128225.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000830 AC: 2AN: 240950Hom.: 0 AF XY: 0.00000765 AC XY: 1AN XY: 130694
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1457612Hom.: 0 Cov.: 32 AF XY: 0.0000152 AC XY: 11AN XY: 724638
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, spondylocheirodysplastic type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces isoleucine with valine at codon 246 of the SLC39A13 protein (p.Ile246Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs767784704, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with SLC39A13-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at