15-44620410-GA-GAA
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_025137.4(SPG11):c.2621-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,582,566 control chromosomes in the GnomAD database, including 7 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0036 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 3 hom. )
Consequence
SPG11
NM_025137.4 splice_region, intron
NM_025137.4 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.681
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 Benign. Variant got -16 ACMG points.
BP6
Variant 15-44620410-G-GA is Benign according to our data. Variant chr15-44620410-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 413993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00358 (542/151388) while in subpopulation AFR AF= 0.0122 (503/41296). AF 95% confidence interval is 0.0113. There are 4 homozygotes in gnomad4. There are 254 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.2621-8dupT | splice_region_variant, intron_variant | Intron 14 of 39 | ENST00000261866.12 | NP_079413.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00359 AC: 543AN: 151274Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00110 AC: 259AN: 234770Hom.: 2 AF XY: 0.000894 AC XY: 114AN XY: 127470
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GnomAD4 exome AF: 0.000419 AC: 600AN: 1431178Hom.: 3 Cov.: 27 AF XY: 0.000386 AC XY: 275AN XY: 713172
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GnomAD4 genome AF: 0.00358 AC: 542AN: 151388Hom.: 4 Cov.: 32 AF XY: 0.00344 AC XY: 254AN XY: 73920
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | SPG11: BP4, BS1, BS2 - |
Hereditary spastic paraplegia 11 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 07, 2025 | - - |
SPG11-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 18, 2024 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 09, 2021 | - - |
Amyotrophic lateral sclerosis type 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Charcot-Marie-Tooth disease axonal type 2X Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at