rs1555454508
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_025137.4(SPG11):c.2912_2914delTACinsGAT(p.IleGln971*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SPG11
NM_025137.4 stop_gained
NM_025137.4 stop_gained
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.35
Genes affected
SPG11 (HGNC:11226): (SPG11 vesicle trafficking associated, spatacsin) The protein encoded by this gene is a potential transmembrane protein that is phosphorylated upon DNA damage. Defects in this gene are a cause of spastic paraplegia type 11 (SPG11). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-44615487-GTA-ATC is Pathogenic according to our data. Variant chr15-44615487-GTA-ATC is described in ClinVar as [Pathogenic]. Clinvar id is 522810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.2912_2914delTACinsGAT | p.IleGln971* | stop_gained | ENST00000261866.12 | NP_079413.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.2912_2914delTACinsGAT | p.IleGln971* | stop_gained | 1 | NM_025137.4 | ENSP00000261866.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 06, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary spastic paraplegia 11 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Nov 22, 2016 | This variant represents a complex allele consisting of a missense change at p.I971 and a stop gain change at p.Q972 acting in cis. It was found [likely] in trans with a pathogenic variant (p.F214fs) in a 23-year-old female with intellectual disability and a progressive motor and cognitive decline. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at