5-894938-G-C

Variant names:

• chr5-894938-G-C
• rs1804865
• NM_004237.4:c.244G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004237.4(TRIP13):​c.244G>C​(p.Val82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V82I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIP13 NM_004237.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 1 publications found

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]

TRIP13 Gene-Disease associations (from GenCC):

• mosaic variegated aneuploidy syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• oocyte maturation defect 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• female infertility due to oocyte meiotic arrest

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• kidney Wilms tumor

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• mosaic variegated aneuploidy syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040343642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP13	NM_004237.4	c.244G>C	p.Val82Leu	missense_variant	Exon 2 of 13	ENST00000166345.8	NP_004228.1
TRIP13	NM_001166260.2	c.244G>C	p.Val82Leu	missense_variant	Exon 2 of 9		NP_001159732.1
TRIP13	XM_011514163.2	c.244G>C	p.Val82Leu	missense_variant	Exon 2 of 14		XP_011512465.1
TRIP13	XM_047417879.1	c.-216G>C		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.244G>C	p.Val82Leu	missense_variant	Exon 2 of 13	1	NM_004237.4	ENSP00000166345.3
TRIP13	ENST00000512024.5	n.359G>C		non_coding_transcript_exon_variant	Exon 2 of 9	1
TRIP13	ENST00000513435.1	c.229G>C	p.Val77Leu	missense_variant	Exon 2 of 8	5		ENSP00000427528.1
TRIP13	ENST00000508456.1	n.218G>C		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.7
DANN	Benign	0.89
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.061
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.12
Sift	Benign	0.71	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.26		Gain of helix (P = 0.062);
MVP		0.31
MPC		0.58
ClinPred		0.020	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.028
gMVP		0.17
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1804865; hg19: chr5-895053;