rs80338714
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 10P and 4B. PVS1_ModeratePP5_Very_StrongBS2
The NM_000047.3(ARSL):c.1743G>A(p.Trp581Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,198,580 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000047.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARSL | NM_000047.3 | c.1743G>A | p.Trp581Ter | stop_gained | 11/11 | ENST00000381134.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSL | ENST00000381134.9 | c.1743G>A | p.Trp581Ter | stop_gained | 11/11 | 1 | NM_000047.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000270 AC: 3AN: 111127Hom.: 0 Cov.: 22 AF XY: 0.0000600 AC XY: 2AN XY: 33335
GnomAD3 exomes AF: 0.00000568 AC: 1AN: 175970Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 61106
GnomAD4 exome AF: 0.0000175 AC: 19AN: 1087453Hom.: 0 Cov.: 29 AF XY: 0.0000169 AC XY: 6AN XY: 354405
GnomAD4 genome ? AF: 0.0000270 AC: 3AN: 111127Hom.: 0 Cov.: 22 AF XY: 0.0000600 AC XY: 2AN XY: 33335
ClinVar
Submissions by phenotype
X-linked chondrodysplasia punctata 1 Pathogenic:6Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2003 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Centogene AG - the Rare Disease Company | - | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Oct 07, 2022 | Criteria applied: PVS1_MOD, PS4, PM2_SUP - |
Pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Feb 05, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Nov 30, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 30, 2023 | - - |
Chondrodysplasia punctata, brachytelephalangic, autosomal Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | This sequence change creates a premature translational stop signal (p.Trp581*) in the ARSE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the ARSE protein. This variant is present in population databases (rs80338714, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with chondrodysplasia punctata (PMID: 9863597, 12567415). ClinVar contains an entry for this variant (Variation ID: 11529). For these reasons, this variant has been classified as Pathogenic. - |
See cases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Feb 18, 2020 | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2023 | Nonsense variant predicted to result in protein truncation as the last 9 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 9863597, 12567415, 26526591, 19839041, 30084160, 32860008, 34529350) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at