chr15-44565920-T-TAAC
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_025137.4(SPG11):c.6932_6933insGTT(p.Thr2311_Met2312insLeu) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T2311T) has been classified as Likely benign.
Frequency
Consequence
NM_025137.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.6932_6933insGTT | p.Thr2311_Met2312insLeu | inframe_insertion | 38/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.6932_6933insGTT | p.Thr2311_Met2312insLeu | inframe_insertion | 38/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250542Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135496
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461662Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727114
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74324
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 29, 2022 | This variant, c.6932_6933insGTT, results in the insertion of 1 amino acid(s) of the SPG11 protein (p.Thr2311_Met2312insLeu), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs747133152, 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: 216773). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 20, 2021 | - - |
Amyotrophic lateral sclerosis type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Charcot-Marie-Tooth disease axonal type 2X Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at