rs746593718
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_003193.5(TBCE):c.1491_1491+4dup variant causes a frameshift change. The variant allele was found at a frequency of 0.0000415 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
TBCE
NM_003193.5 frameshift
NM_003193.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.77
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]
B3GALNT2 (HGNC:28596): (beta-1,3-N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.53 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-235448437-C-CAAAGT is Pathogenic according to our data. Variant chr1-235448437-C-CAAAGT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 520625.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBCE | NM_003193.5 | c.1491_1491+4dup | frameshift_variant | 16/17 | ENST00000642610.2 | ||
B3GALNT2 | NM_152490.5 | c.*1768_*1769insACTTT | 3_prime_UTR_variant | 12/12 | ENST00000366600.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBCE | ENST00000642610.2 | c.1491_1491+4dup | frameshift_variant | 16/17 | NM_003193.5 | P1 | |||
B3GALNT2 | ENST00000366600.8 | c.*1768_*1769insACTTT | 3_prime_UTR_variant | 12/12 | 1 | NM_152490.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152056Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251438Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135908
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GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461728Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727186
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2015 | Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected - |
Autosomal recessive Kenny-Caffey syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Jun 21, 2022 | - - |
Computational scores
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Name
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at