rs867562406
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_031206.7(LAS1L):āc.1082C>Gā(p.Pro361Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000495 in 525,110 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P361P) has been classified as Uncertain significance.
Frequency
Consequence
NM_031206.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAS1L | NM_031206.7 | c.1082C>G | p.Pro361Arg | missense_variant | 9/14 | ENST00000374811.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAS1L | ENST00000374811.8 | c.1082C>G | p.Pro361Arg | missense_variant | 9/14 | 1 | NM_031206.7 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111689Hom.: 0 Cov.: 22 AF XY: 0.0000295 AC XY: 1AN XY: 33883
GnomAD4 exome AF: 0.0000581 AC: 24AN: 413367Hom.: 0 Cov.: 0 AF XY: 0.0000788 AC XY: 12AN XY: 152349
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111743Hom.: 0 Cov.: 22 AF XY: 0.0000295 AC XY: 1AN XY: 33947
ClinVar
Submissions by phenotype
Wilson-Turner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2019 | This variant has not been reported in the literature in individuals with LAS1L-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 361 of the LAS1L protein (p.Pro361Arg). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and arginine. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | LAS1L: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at