9-127487680-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001005373.4(LRSAM1):c.1264G>A(p.Ala422Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A422S) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.1264G>A | p.Ala422Thr | missense_variant | 18/26 | ENST00000300417.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRSAM1 | ENST00000300417.11 | c.1264G>A | p.Ala422Thr | missense_variant | 18/26 | 1 | NM_001005373.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152210Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250244Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135266
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461080Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726764
GnomAD4 genome AF: 0.000112 AC: 17AN: 152210Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | The c.1264G>A (p.A422T) alteration is located in exon 17 (coding exon 16) of the LRSAM1 gene. This alteration results from a G to A substitution at nucleotide position 1264, causing the alanine (A) at amino acid position 422 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease axonal type 2P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 422 of the LRSAM1 protein (p.Ala422Thr). This variant is present in population databases (rs372452916, gnomAD 0.03%). 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: 2050470). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at