chr4-154744366-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_004744.5(LRAT):c.40G>T(p.Glu14*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,032 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 (★).
Frequency
Consequence
NM_004744.5 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRAT | NM_004744.5 | c.40G>T | p.Glu14* | stop_gained | Exon 2 of 3 | ENST00000336356.4 | NP_004735.2 | |
LRAT | NM_001301645.2 | c.40G>T | p.Glu14* | stop_gained | Exon 2 of 3 | NP_001288574.1 | ||
LRAT | XM_047416405.1 | c.40G>T | p.Glu14* | stop_gained | Exon 2 of 3 | XP_047272361.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727236
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
Leber congenital amaurosis Pathogenic:1
The p.Glu14X variant in LRAT has not been previously reported in individuals wit h Leber congenital amaurosis and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 14, which is predicted to lead to a truncated or absent protein. Loss of function of the LRA T gene is strongly associated with autosomal recessive Leber congenital amaurosi s. In summary, although additional studies are required to fully establish its c linical significance, this variant meets criteria to be classified as likely pat hogenic for Leber congenital amaurosis in an autosomal recessive manner. ACMG/AM P Criteria applied: PVS1_Strong, PM2. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at