Variant 5-893075-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_004237.4(TRIP13):c.77A>T(p.His26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,444,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. H26R) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

TRIP13
NM_004237.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.936

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]

TRIP13 links:

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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;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr5-893075-A-G is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.124539495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP13	NM_004237.4 link	c.77A>T	p.His26Leu	missense_variant	Exon 1 of 13	ENST00000166345.8	NP_004228.1	Q15645-1
TRIP13	NM_001166260.2 link	c.77A>T	p.His26Leu	missense_variant	Exon 1 of 9		NP_001159732.1
TRIP13	XM_011514163.2 link	c.77A>T	p.His26Leu	missense_variant	Exon 1 of 14		XP_011512465.1	Q15645-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIP13	ENST00000166345.8 link	c.77A>T	p.His26Leu	missense_variant	Exon 1 of 13	1	NM_004237.4	ENSP00000166345.3	Q15645-1
TRIP13	ENST00000512024.5 link	n.192A>T		non_coding_transcript_exon_variant	Exon 1 of 9	1
TRIP13	ENST00000508456.1 link	n.51A>T		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000460

AC:

AN:

217592

Hom.:

AF XY:

0.00000836

AC XY:

AN XY:

119632

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1444434

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000511

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000837

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.10

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.46

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.68

REVEL

Benign

0.20

Sift

Benign

0.68

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.14

MutPred

0.37

Loss of disorder (P = 0.0308);

MVP

0.16

MPC

0.73

ClinPred

0.021

GERP RS

-4.6

Varity_R

0.14

gMVP

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over