rs121908678
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003982.4(SLC7A7):c.1228C>T(p.Arg410Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,878 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R410R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003982.4 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 |
---|---|---|---|---|---|---|---|
SLC7A7 | NM_003982.4 | c.1228C>T | p.Arg410Ter | stop_gained | 8/10 | ENST00000674313.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC7A7 | ENST00000674313.1 | c.1228C>T | p.Arg410Ter | stop_gained | 8/10 | NM_003982.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251312Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135828
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727240
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Lysinuric protein intolerance Pathogenic:3Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 17, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 11, 2023 | This sequence change creates a premature translational stop signal (p.Arg410*) in the SLC7A7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC7A7 are known to be pathogenic (PMID: 10631139, 17764084). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 6212). This premature translational stop signal has been observed in individual(s) with lysinuric protein intolerance (PMID: 10980538, 26865117). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121908678, gnomAD 0.0009%). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2008 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at