rs80338869
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_025137.4(SPG11):c.7023C>T(p.Tyr2341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,613,970 control chromosomes in the GnomAD database, including 655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.019 ( 31 hom., cov: 32)
Exomes 𝑓: 0.026 ( 624 hom. )
Consequence
SPG11
NM_025137.4 synonymous
NM_025137.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.05
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 -9 ACMG points.
BP6
?
Variant 15-44564675-G-A is Benign according to our data. Variant chr15-44564675-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 41357.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}. Variant chr15-44564675-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0189 (2878/152250) while in subpopulation NFE AF= 0.0286 (1944/68014). AF 95% confidence interval is 0.0275. There are 31 homozygotes in gnomad4. There are 1309 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 31 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.7023C>T | p.Tyr2341= | synonymous_variant | 39/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.7023C>T | p.Tyr2341= | synonymous_variant | 39/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0189 AC: 2879AN: 152132Hom.: 31 Cov.: 32
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GnomAD3 exomes AF: 0.0205 AC: 5158AN: 251064Hom.: 73 AF XY: 0.0209 AC XY: 2837AN XY: 135784
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GnomAD4 exome AF: 0.0265 AC: 38725AN: 1461720Hom.: 624 Cov.: 32 AF XY: 0.0265 AC XY: 19252AN XY: 727174
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GnomAD4 genome ? AF: 0.0189 AC: 2878AN: 152250Hom.: 31 Cov.: 32 AF XY: 0.0176 AC XY: 1309AN XY: 74452
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 10, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Jun 22, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2016 | 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. - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 18, 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
DS_AG_spliceai
Position offset: -14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at