5-893011-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_004237.4(TRIP13):​c.13G>T​(p.Val5Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000128 in 1,563,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TRIP13
NM_004237.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.19
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033236235).
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000113 (16/1413428) while in subpopulation AMR AF= 0.000402 (16/39838). AF 95% confidence interval is 0.000252. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIP13NM_004237.4 linkc.13G>T p.Val5Leu missense_variant Exon 1 of 13 ENST00000166345.8 NP_004228.1 Q15645-1
TRIP13NM_001166260.2 linkc.13G>T p.Val5Leu missense_variant Exon 1 of 9 NP_001159732.1
TRIP13XM_011514163.2 linkc.13G>T p.Val5Leu missense_variant Exon 1 of 14 XP_011512465.1 Q15645-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIP13ENST00000166345.8 linkc.13G>T p.Val5Leu missense_variant Exon 1 of 13 1 NM_004237.4 ENSP00000166345.3 Q15645-1
TRIP13ENST00000512024.5 linkn.128G>T non_coding_transcript_exon_variant Exon 1 of 9 1
TRIP13ENST00000508456.1 linkn.-14G>T upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000267
AC:
4
AN:
149968
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000265
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000737
AC:
14
AN:
189882
Hom.:
0
AF XY:
0.0000478
AC XY:
5
AN XY:
104656
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000478
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000113
AC:
16
AN:
1413428
Hom.:
0
Cov.:
31
AF XY:
0.00000998
AC XY:
7
AN XY:
701448
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000402
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000267
AC:
4
AN:
149968
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73192
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000265
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000421
AC:
5

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Oct 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 5 of the TRIP13 protein (p.Val5Leu). This variant is present in population databases (rs759352780, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TRIP13-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Benign
0.93
DEOGEN2
Benign
0.098
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.34
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.77
T
M_CAP
Pathogenic
0.98
D
MetaRNN
Benign
0.033
T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.45
N
REVEL
Benign
0.25
Sift
Benign
0.15
T
Sift4G
Benign
0.15
T
Polyphen
0.0
B
Vest4
0.17
MutPred
0.18
Gain of helix (P = 0.062);
MVP
0.28
MPC
0.59
ClinPred
0.062
T
GERP RS
3.0
Varity_R
0.10
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs759352780; hg19: chr5-893126; API