5-893094-A-AG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004237.4(TRIP13):​c.92+5dupG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000957 in 1,587,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

TRIP13
NM_004237.4 splice_region, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIP13NM_004237.4 linkc.92+5dupG splice_region_variant, intron_variant Intron 1 of 12 ENST00000166345.8 NP_004228.1 Q15645-1
TRIP13NM_001166260.2 linkc.92+5dupG splice_region_variant, intron_variant Intron 1 of 8 NP_001159732.1
TRIP13XM_011514163.2 linkc.92+5dupG 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+4_92+5insG splice_region_variant, intron_variant Intron 1 of 12 1 NM_004237.4 ENSP00000166345.3 Q15645-1
TRIP13ENST00000512024.5 linkn.207+4_207+5insG splice_region_variant, intron_variant Intron 1 of 8 1
TRIP13ENST00000508456.1 linkn.66+4_66+5insG splice_region_variant, intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.0000857
AC:
13
AN:
151766
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000493
AC:
10
AN:
202984
Hom.:
0
AF XY:
0.0000359
AC XY:
4
AN XY:
111518
show subpopulations
Gnomad AFR exome
AF:
0.000166
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:
0.0000871
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000968
AC:
139
AN:
1435994
Hom.:
0
Cov.:
31
AF XY:
0.0000869
AC XY:
62
AN XY:
713080
show subpopulations
Gnomad4 AFR exome
AF:
0.0000907
Gnomad4 AMR exome
AF:
0.0000235
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:
0.000119
Gnomad4 OTH exome
AF:
0.0000503
GnomAD4 genome
AF:
0.0000856
AC:
13
AN:
151882
Hom.:
0
Cov.:
32
AF XY:
0.0000808
AC XY:
6
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000907

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Sep 14, 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 (rs762118615, gnomAD 0.01%). 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
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: rs762118615; hg19: chr5-893209; API