5-893096-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004237.4(TRIP13):​c.92+6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 1,583,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

TRIP13
NM_004237.4 splice_region, intron

Scores

2
Splicing: ADA: 0.0007542
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.0520
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIP13NM_004237.4 linkc.92+6C>G splice_region_variant, intron_variant Intron 1 of 12 ENST00000166345.8 NP_004228.1 Q15645-1
TRIP13NM_001166260.2 linkc.92+6C>G splice_region_variant, intron_variant Intron 1 of 8 NP_001159732.1
TRIP13XM_011514163.2 linkc.92+6C>G splice_region_variant, intron_variant Intron 1 of 13 XP_011512465.1 Q15645-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIP13ENST00000166345.8 linkc.92+6C>G splice_region_variant, intron_variant Intron 1 of 12 1 NM_004237.4 ENSP00000166345.3 Q15645-1
TRIP13ENST00000512024.5 linkn.207+6C>G splice_region_variant, intron_variant Intron 1 of 8 1
TRIP13ENST00000508456.1 linkn.66+6C>G splice_region_variant, intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000103
AC:
2
AN:
194928
Hom.:
0
AF XY:
0.00000935
AC XY:
1
AN XY:
106960
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000228
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000489
AC:
70
AN:
1430954
Hom.:
0
Cov.:
31
AF XY:
0.0000521
AC XY:
37
AN XY:
710188
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000625
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jun 10, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change falls in intron 1 of the TRIP13 gene. It does not directly change the encoded amino acid sequence of the TRIP13 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TRIP13-related conditions. 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. -

TRIP13-related disorder Benign:1
Oct 05, 2020
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
11
DANN
Benign
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00075
dbscSNV1_RF
Benign
0.038
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs948268218; hg19: chr5-893211; API