rs149592537
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001080442.3(SLC38A8):c.598C>T(p.Gln200Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,068 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001080442.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC38A8 | NM_001080442.3 | c.598C>T | p.Gln200Ter | stop_gained | 5/11 | ENST00000299709.8 | |
SLC38A8 | XM_017022946.1 | c.598C>T | p.Gln200Ter | stop_gained | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC38A8 | ENST00000299709.8 | c.598C>T | p.Gln200Ter | stop_gained | 5/11 | 5 | NM_001080442.3 | P1 | |
SLC38A8 | ENST00000568178.1 | c.598C>T | p.Gln200Ter | stop_gained | 5/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251198Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135788
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727200
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74394
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change creates a premature translational stop signal (p.Gln200*) in the SLC38A8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC38A8 are known to be pathogenic (PMID: 24290379). This variant is present in population databases (rs149592537, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of SLC38A8-related conditions (PMID: 24290379, 35029636). ClinVar contains an entry for this variant (Variation ID: 125447). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Foveal hypoplasia 2 and optic nerve misrouting with or without anterior segment dysgenesis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 05, 2013 | - - |
Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 23, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at