rs767784704
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001128225.3(SLC39A13):āc.736A>Gā(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 (ā ). 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