9-127454489-G-GC
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001005373.4(LRSAM1):c.-32-3dup variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,610,190 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_001005373.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.-32-3dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000300417.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRSAM1 | ENST00000300417.11 | c.-32-3dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001005373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1457986Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 725536
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genomics Laboratory, Washington University in St. Louis | Nov 08, 2023 | The LRSAM1 c.-32-3dup intronic variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors indicate that the variant has no impact on splicing, evidence that this variant does not have a damaging effect on LRSAM1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at