GeneBe

5-914504-C-T

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_004237.4(TRIP13):​c.1060C>T​(p.Arg354*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRIP13
NM_004237.4 stop_gained

Scores

2
3
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.07

Publications

5 publications found
Variant links:
Genes affected
TRIP13 (HGNC:12307): (thyroid hormone receptor interactor 13) This gene encodes a protein that interacts with thyroid hormone receptors, also known as hormone-dependent transcription factors. The gene product interacts specifically with the ligand binding domain. This gene is one of several that may play a role in early-stage non-small cell lung cancer. [provided by RefSeq, Oct 2009]
TRIP13 Gene-Disease associations (from GenCC):
  • mosaic variegated aneuploidy syndrome 3
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
  • oocyte maturation defect 9
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • female infertility due to oocyte meiotic arrest
    Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
  • kidney Wilms tumor
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • mosaic variegated aneuploidy syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 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 5-914504-C-T is Pathogenic according to our data. Variant chr5-914504-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 431045.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIP13NM_004237.4 linkc.1060C>T p.Arg354* stop_gained Exon 11 of 13 ENST00000166345.8 NP_004228.1 Q15645-1
TRIP13XM_011514163.2 linkc.1060C>T p.Arg354* stop_gained Exon 11 of 14 XP_011512465.1 Q15645-1
TRIP13XM_047417879.1 linkc.601C>T p.Arg201* stop_gained Exon 11 of 13 XP_047273835.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIP13ENST00000166345.8 linkc.1060C>T p.Arg354* stop_gained Exon 11 of 13 1 NM_004237.4 ENSP00000166345.3 Q15645-1
TRIP13ENST00000510412.5 linkn.-55C>T upstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461282
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726978
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52978
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111894
Other (OTH)
AF:
0.00
AC:
0
AN:
60382
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.022510), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Mosaic variegated aneuploidy syndrome 3 Pathogenic:1
Jul 27, 2017
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
38
DANN
Uncertain
1.0
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Benign
0.29
N
PhyloP100
1.1
Vest4
0.97
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=8/192
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.35
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.35
Position offset: -39

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs376882637; hg19: chr5-914619; COSMIC: COSV51320113; COSMIC: COSV51320113; API