chr1-235380155-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_003193.5(TBCE):c.100+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,536,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00063 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000065 ( 0 hom. )
Consequence
TBCE
NM_003193.5 splice_donor_region, intron
NM_003193.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00002739
2
Clinical Significance
Conservation
PhyloP100: 0.589
Genes affected
TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 1-235380155-C-T is Benign according to our data. Variant chr1-235380155-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 595734.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000625 (91/145540) while in subpopulation AFR AF= 0.00209 (82/39322). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBCE | NM_003193.5 | c.100+6C>T | splice_donor_region_variant, intron_variant | ENST00000642610.2 | |||
TBCE | NM_001079515.3 | c.100+6C>T | splice_donor_region_variant, intron_variant | ||||
TBCE | NM_001287801.2 | c.100+6C>T | splice_donor_region_variant, intron_variant | ||||
TBCE | NM_001287802.2 | c.-211+6C>T | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBCE | ENST00000642610.2 | c.100+6C>T | splice_donor_region_variant, intron_variant | NM_003193.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000605 AC: 88AN: 145428Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000141 AC: 35AN: 248602Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 134498
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GnomAD4 exome AF: 0.0000654 AC: 91AN: 1390884Hom.: 0 Cov.: 30 AF XY: 0.0000605 AC XY: 42AN XY: 694624
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change falls in intron 2 of the TBCE gene. It does not directly change the encoded amino acid sequence of the TBCE protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs182896657, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with TBCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 595734). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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 | Eurofins Ntd Llc (ga) | Jan 26, 2018 | - - |
TBCE-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 12, 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). - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at