NM_001128225.3:c.640A>G
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001128225.3(SLC39A13):c.640A>G(p.Ile214Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000991 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. I214I) has been classified as Likely benign.
Frequency
Consequence
NM_001128225.3 missense
Scores
Clinical Significance
Conservation
Publications
- Ehlers-Danlos syndrome, spondylocheirodysplastic typeInheritance: 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 syndromeInheritance: AR Classification: DEFINITIVE Submitted by: G2P
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000319 AC: 8AN: 250526 AF XY: 0.0000295 show subpopulations
GnomAD4 exome AF: 0.000106 AC: 155AN: 1461756Hom.: 0 Cov.: 34 AF XY: 0.0000990 AC XY: 72AN XY: 727198 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74380 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function -
Inborn genetic diseases Uncertain:1
The c.640A>G (p.I214V) alteration is located in exon 5 (coding exon 4) of the SLC39A13 gene. This alteration results from a A to G substitution at nucleotide position 640, causing the isoleucine (I) at amino acid position 214 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Ehlers-Danlos syndrome, spondylocheirodysplastic type Uncertain:1
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 214 of the SLC39A13 protein (p.Ile214Val). This variant is present in population databases (rs750123189, gnomAD 0.005%). 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: 452828). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC39A13 protein function. 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