rs145881988
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001005373.4(LRSAM1):c.962G>A(p.Arg321Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,611,702 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R321W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001005373.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.962G>A | p.Arg321Gln | missense_variant | 14/26 | ENST00000300417.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRSAM1 | ENST00000300417.11 | c.962G>A | p.Arg321Gln | missense_variant | 14/26 | 1 | NM_001005373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000323 AC: 8AN: 247310Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134588
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1459414Hom.: 0 Cov.: 35 AF XY: 0.0000275 AC XY: 20AN XY: 726084
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74466
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2022 | The p.R321Q variant (also known as c.962G>A), located in coding exon 12 of the LRSAM1 gene, results from a G to A substitution at nucleotide position 962. The arginine at codon 321 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant Charcot-Marie-Tooth disease, type 2P (CMT2P); however, its contribution to the development of autosomal recessive CMT2P is uncertain. - |
Charcot-Marie-Tooth disease axonal type 2P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 408265). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. This variant is present in population databases (rs145881988, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 321 of the LRSAM1 protein (p.Arg321Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at