rs780868977
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM2PP3_StrongBP6
The NM_001005373.4(LRSAM1):c.1043+5G>A variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.0000124 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001005373.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.1043+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000300417.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRSAM1 | ENST00000300417.11 | c.1043+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_001005373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251344Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135874
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461880Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 727246
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 13, 2023 | This sequence change falls in intron 13 of the LRSAM1 gene. It does not directly change the encoded amino acid sequence of the LRSAM1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs780868977, gnomAD 0.006%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 472788). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | LRSAM1: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at