chr9-127461243-C-T
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BP6
The NM_001005373.4(LRSAM1):c.392C>T(p.Thr131Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,611,774 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
Publications
- Charcot-Marie-Tooth disease axonal type 2PInheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.392C>T | p.Thr131Ile | missense_variant | Exon 8 of 26 | ENST00000300417.11 | NP_001005373.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0000477 AC: 12AN: 251480 AF XY: 0.0000662 show subpopulations
GnomAD4 exome AF: 0.0000343 AC: 50AN: 1459530Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 726062 show subpopulations
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74382 show subpopulations
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
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Charcot-Marie-Tooth disease axonal type 2P Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 131 of the LRSAM1 protein (p.Thr131Ile). This variant is present in population databases (rs772202137, gnomAD 0.009%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 540007). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LRSAM1 protein function with a negative predictive value of 80%. 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. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at