5-894792-C-T

Variant names:

• chr5-894792-C-T
• NM_004237.4:c.98C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004237.4(TRIP13):​c.98C>T​(p.Ala33Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIP13 NM_004237.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

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]

ACMG classification

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 (MetaRNN=0.26104861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP13	NM_004237.4	c.98C>T	p.Ala33Val	missense_variant	Exon 2 of 13	ENST00000166345.8	NP_004228.1
TRIP13	NM_001166260.2	c.98C>T	p.Ala33Val	missense_variant	Exon 2 of 9		NP_001159732.1
TRIP13	XM_011514163.2	c.98C>T	p.Ala33Val	missense_variant	Exon 2 of 14		XP_011512465.1
TRIP13	XM_047417879.1	c.-362C>T		5_prime_UTR_variant	Exon 2 of 13		XP_047273835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP13	ENST00000166345.8	c.98C>T	p.Ala33Val	missense_variant	Exon 2 of 13	1	NM_004237.4	ENSP00000166345.3
TRIP13	ENST00000512024.5	n.213C>T		non_coding_transcript_exon_variant	Exon 2 of 9	1
TRIP13	ENST00000513435.1	c.83C>T	p.Ala28Val	missense_variant	Exon 2 of 8	5		ENSP00000427528.1
TRIP13	ENST00000508456.1	n.72C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443666 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 716466

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: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Sep 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 33 of the TRIP13 protein (p.Ala33Val). 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	0.15
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.97	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Benign	0.27	T
Polyphen		0.97	D
Vest4		0.27
MutPred		0.16		Loss of ubiquitination at K34 (P = 0.0272);
MVP		0.29
MPC		0.62
ClinPred		0.89	D
GERP RS		5.2
Varity_R		0.38
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-894907;