rs139314486
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_014844.5(TECPR2):c.4089G>A(p.Ala1363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,613,388 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 9 hom. )
Consequence
TECPR2
NM_014844.5 synonymous
NM_014844.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.927
Genes affected
TECPR2 (HGNC:19957): (tectonin beta-propeller repeat containing 2) The protein encoded by this gene is a member of the tectonin beta-propeller repeat-containing (TECPR) family, and contains both TECPR and tryptophan-aspartic acid repeat (WD repeat) domains. This gene has been implicated in autophagy, as reduced expression levels of this gene have been associated with impaired autophagy. Recessive mutations in this gene have been associated with a hereditary form of spastic paraparesis (HSP). HSP is characterized by progressive spasticity and paralysis of the legs. There is also some evidence linking mutations in this gene with birdshot chorioretinopathy (BSCR), which results in inflammation of the choroid and retina. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 14-102498110-G-A is Benign according to our data. Variant chr14-102498110-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 385226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102498110-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.927 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECPR2 | NM_014844.5 | c.4089G>A | p.Ala1363= | synonymous_variant | 20/20 | ENST00000359520.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.4089G>A | p.Ala1363= | synonymous_variant | 20/20 | 1 | NM_014844.5 | P1 | |
TECPR2 | ENST00000559124.1 | n.189G>A | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
TECPR2 | ENST00000561099.1 | n.398G>A | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00133 AC: 202AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00152 AC: 378AN: 249462Hom.: 0 AF XY: 0.00159 AC XY: 215AN XY: 135042
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GnomAD4 exome AF: 0.00206 AC: 3008AN: 1461078Hom.: 9 Cov.: 37 AF XY: 0.00206 AC XY: 1494AN XY: 726848
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GnomAD4 genome ? AF: 0.00133 AC: 202AN: 152310Hom.: 0 Cov.: 33 AF XY: 0.00134 AC XY: 100AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 23, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | TECPR2: BP4, BP7 - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 01, 2018 | - - |
TECPR2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 10, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary spastic paraplegia 49 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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