rs1085307101
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004239.4(TRIP11):c.2498_2501delAATA(p.Lys833IlefsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TRIP11
NM_004239.4 frameshift
NM_004239.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.55
Publications
0 publications found
Genes affected
TRIP11 (HGNC:12305): (thyroid hormone receptor interactor 11) This gene was identified based on the interaction of its protein product with thyroid hormone receptor beta. This protein is associated with the Golgi apparatus. The N-terminal region of the protein binds Golgi membranes and the C-terminal region binds the minus ends of microtubules; thus, the protein is thought to play a role in assembly and maintenance of the Golgi ribbon structure around the centrosome. Mutations in this gene cause achondrogenesis type IA.[provided by RefSeq, Mar 2010]
TRIP11 Gene-Disease associations (from GenCC):
- achondrogenesis type IAInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet
- TRIP11-related skeletal dysplasiaInheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-92005474-ATATT-A is Pathogenic according to our data. Variant chr14-92005474-ATATT-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 225501.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004239.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TRIP11 | TSL:1 MANE Select | c.2498_2501delAATA | p.Lys833IlefsTer5 | frameshift | Exon 11 of 21 | ENSP00000267622.4 | Q15643-1 | ||
| TRIP11 | TSL:1 | c.1643_1646delAATA | p.Lys548fs | frameshift | Exon 5 of 15 | ENSP00000451032.1 | H0YJ97 | ||
| TRIP11 | c.2495_2498delAATA | p.Lys832IlefsTer5 | frameshift | Exon 11 of 21 | ENSP00000583204.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461742Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727162 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461742
Hom.:
AF XY:
AC XY:
0
AN XY:
727162
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86218
European-Finnish (FIN)
AF:
AC:
0
AN:
53366
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111994
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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10
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Achondrogenesis, type IA (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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