16-84022883-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_ModeratePP5_Moderate
The NM_001080442.3(SLC38A8):c.697G>A(p.Glu233Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,602,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E233G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001080442.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC38A8 | NM_001080442.3 | c.697G>A | p.Glu233Lys | missense_variant | 7/11 | ENST00000299709.8 | |
SLC38A8 | XM_017022946.1 | c.697G>A | p.Glu233Lys | missense_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC38A8 | ENST00000299709.8 | c.697G>A | p.Glu233Lys | missense_variant | 7/11 | 5 | NM_001080442.3 | P1 | |
SLC38A8 | ENST00000568178.1 | c.697G>A | p.Glu233Lys | missense_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152132Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000766 AC: 18AN: 234948Hom.: 0 AF XY: 0.0000628 AC XY: 8AN XY: 127304
GnomAD4 exome AF: 0.0000303 AC: 44AN: 1449896Hom.: 0 Cov.: 31 AF XY: 0.0000264 AC XY: 19AN XY: 721030
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152132Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 233 of the SLC38A8 protein (p.Glu233Lys). This variant is present in population databases (rs372929441, gnomAD 0.03%). This missense change has been observed in individual(s) with foveal hypoplasia (PMID: 24290379, 33594928, 33781268). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 125446). 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 expected to disrupt SLC38A8 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. - |
Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 05, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at