9-127454528-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001384144.1(LRSAM1):c.-784A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000205 in 1,461,812 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 Uncertain significance (★).
Frequency
Consequence
NM_001384144.1 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.1A>T | p.Met1? | initiator_codon_variant | Exon 3 of 26 | ENST00000300417.11 | NP_001005373.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251110Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135762
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727216
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2P Uncertain:1
This sequence change affects the initiator methionine of the LRSAM1 mRNA. The next in-frame methionine is located at codon 22. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1404383). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at