rs11559075
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003119.4(SPG7):c.2280G>A(p.Pro760=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,613,870 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 14 hom., cov: 32)
Exomes 𝑓: 0.013 ( 144 hom. )
Consequence
SPG7
NM_003119.4 synonymous
NM_003119.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.03
Genes affected
SPG7 (HGNC:11237): (SPG7 matrix AAA peptidase subunit, paraplegin) This gene encodes a mitochondrial metalloprotease protein that is a member of the AAA family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. Mutations in this gene cause autosomal recessive spastic paraplegia 7. Two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 16-89556985-G-A is Benign according to our data. Variant chr16-89556985-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89556985-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.03 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0104 (1579/152306) while in subpopulation EAS AF= 0.0178 (92/5176). AF 95% confidence interval is 0.0148. There are 14 homozygotes in gnomad4. There are 743 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG7 | NM_003119.4 | c.2280G>A | p.Pro760= | synonymous_variant | 17/17 | ENST00000645818.2 | |
SPG7 | XM_047434540.1 | c.966G>A | p.Pro322= | synonymous_variant | 9/9 | ||
SPG7 | NM_001363850.1 | c.*58G>A | 3_prime_UTR_variant | 18/18 | |||
SPG7 | XM_047434537.1 | c.*58G>A | 3_prime_UTR_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG7 | ENST00000645818.2 | c.2280G>A | p.Pro760= | synonymous_variant | 17/17 | NM_003119.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0104 AC: 1577AN: 152188Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.0126 AC: 3159AN: 251310Hom.: 20 AF XY: 0.0118 AC XY: 1606AN XY: 135874
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GnomAD4 exome AF: 0.0133 AC: 19375AN: 1461564Hom.: 144 Cov.: 31 AF XY: 0.0130 AC XY: 9456AN XY: 727082
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GnomAD4 genome ? AF: 0.0104 AC: 1579AN: 152306Hom.: 14 Cov.: 32 AF XY: 0.00998 AC XY: 743AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 7 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 20, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at