rs757237014
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_025137.4(SPG11):βc.6508_6510delβ(p.Asn2170del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000562 in 1,601,668 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ). Synonymous variant affecting the same amino acid position (i.e. N2170N) has been classified as Likely benign.
Frequency
Genomes: π 0.000033 ( 0 hom., cov: 31)
Exomes π: 0.0000028 ( 0 hom. )
Consequence
SPG11
NM_025137.4 inframe_deletion
NM_025137.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.79
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
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Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_025137.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.6508_6510del | p.Asn2170del | inframe_deletion | 35/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.6508_6510del | p.Asn2170del | inframe_deletion | 35/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000131 AC: 3AN: 229000Hom.: 0 AF XY: 0.0000163 AC XY: 2AN XY: 123062
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GnomAD4 exome AF: 0.00000276 AC: 4AN: 1449502Hom.: 0 AF XY: 0.00000139 AC XY: 1AN XY: 719720
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74348
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 22, 2022 | This variant, c.6508_6510del, results in the deletion of 1 amino acid(s) of the SPG11 protein (p.Asn2170del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs757237014, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 406522). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 8
Find out detailed SpliceAI scores and Pangolin per-transcript scores at