chr9-127502789-C-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The NM_001005373.4(LRSAM1):c.2062C>A(p.Leu688Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,612,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001005373.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.2062C>A | p.Leu688Ile | missense_variant | Exon 26 of 26 | ENST00000300417.11 | NP_001005373.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152100Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000234 AC: 58AN: 247492Hom.: 0 AF XY: 0.000156 AC XY: 21AN XY: 134566
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1460644Hom.: 0 Cov.: 34 AF XY: 0.0000413 AC XY: 30AN XY: 726608
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152100Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74314
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.L688I variant (also known as c.2062C>A), located in coding exon 24 of the LRSAM1 gene, results from a C to A substitution at nucleotide position 2062. The leucine at codon 688 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on population data from Genome Aggregation Consortium (gnomAD), the p.L688I variant has an overall frequency of 0.02116% (59/278788 total alleles studied) without any homozygous individuals observed. The highest observed sub-population frequency was 0.1616% (57/35264 total alleles studied) in the Latino cochort. Therefore, this variant is considered to be likely benign for dominantly inherited LRSAM1-related neuropathy but is still rare enough to potentially be disease causing for recessively inherited LRSAM1-related neuropathy. Since supporting evidence for recessive neuropathy is limited at this time, the clinical significance of this alteration remains unclear. -
Charcot-Marie-Tooth disease axonal type 2P Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at