NM_004237.4:c.232A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004237.4(TRIP13):​c.232A>G​(p.Thr78Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,196 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 0.000013 ( 0 hom., cov: 32)

Consequence

TRIP13
NM_004237.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27809086).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIP13NM_004237.4 linkc.232A>G p.Thr78Ala missense_variant Exon 2 of 13 ENST00000166345.8 NP_004228.1 Q15645-1
TRIP13NM_001166260.2 linkc.232A>G p.Thr78Ala missense_variant Exon 2 of 9 NP_001159732.1
TRIP13XM_011514163.2 linkc.232A>G p.Thr78Ala missense_variant Exon 2 of 14 XP_011512465.1 Q15645-1
TRIP13XM_047417879.1 linkc.-228A>G 5_prime_UTR_variant Exon 2 of 13 XP_047273835.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIP13ENST00000166345.8 linkc.232A>G p.Thr78Ala missense_variant Exon 2 of 13 1 NM_004237.4 ENSP00000166345.3 Q15645-1
TRIP13ENST00000512024.5 linkn.347A>G non_coding_transcript_exon_variant Exon 2 of 9 1
TRIP13ENST00000513435.1 linkc.217A>G p.Thr73Ala missense_variant Exon 2 of 8 5 ENSP00000427528.1 H0YAL2
TRIP13ENST00000508456.1 linkn.206A>G non_coding_transcript_exon_variant Exon 2 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jan 28, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 78 of the TRIP13 protein (p.Thr78Ala). This variant is not present in population databases (gnomAD no frequency). 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
0.12
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.0072
Eigen_PC
Benign
0.12
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.038
Sift
Benign
0.041
D
Sift4G
Benign
0.37
T
Polyphen
0.15
B
Vest4
0.56
MutPred
0.28
Loss of helix (P = 0.1299);
MVP
0.23
MPC
0.59
ClinPred
0.59
D
GERP RS
5.0
Varity_R
0.12
gMVP
0.40

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: rs1211397398; hg19: chr5-895041; API