8-22404768-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The ENST00000381237.6(SLC39A14):c.58G>A(p.Gly20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G20C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000381237.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC39A14 | NM_001128431.4 | c.58G>A | p.Gly20Ser | missense_variant | 2/9 | ENST00000381237.6 | NP_001121903.1 | |
SLC39A14 | NM_015359.6 | c.58G>A | p.Gly20Ser | missense_variant | 2/9 | ENST00000359741.10 | NP_056174.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC39A14 | ENST00000359741.10 | c.58G>A | p.Gly20Ser | missense_variant | 2/9 | 2 | NM_015359.6 | ENSP00000352779 | A2 | |
SLC39A14 | ENST00000381237.6 | c.58G>A | p.Gly20Ser | missense_variant | 2/9 | 1 | NM_001128431.4 | ENSP00000370635 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461632Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 727146
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | SLC39A14: PM2, BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 08, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 20 of the SLC39A14 protein (p.Gly20Ser). 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. 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 serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1470060). This variant has not been reported in the literature in individuals affected with SLC39A14-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.