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

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate

The NM_004237.4(TRIP13):c.77A>G(p.His26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,444,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TRIP13
NM_004237.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

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 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 5-893075-A-G is Pathogenic according to our data. Variant chr5-893075-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 977641.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-893075-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIP13	NM_004237.4 linkuse as main transcript	c.77A>G	p.His26Arg	missense_variant	1/13	ENST00000166345.8	NP_004228.1
TRIP13	NM_001166260.2 linkuse as main transcript	c.77A>G	p.His26Arg	missense_variant	1/9		NP_001159732.1
TRIP13	XM_011514163.2 linkuse as main transcript	c.77A>G	p.His26Arg	missense_variant	1/14		XP_011512465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP13	ENST00000166345.8 linkuse as main transcript	c.77A>G	p.His26Arg	missense_variant	1/13	1	NM_004237.4	ENSP00000166345	P1	Q15645-1
TRIP13	ENST00000512024.5 linkuse as main transcript	n.192A>G		non_coding_transcript_exon_variant	1/9	1
TRIP13	ENST00000508456.1 linkuse as main transcript	n.51A>G		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000919

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:

0.0000306

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:

0.000183

GnomAD4 exome

AF:

0.00000485

AC:

AN:

1444434

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

717804

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000459

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000489

Hom.:

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oocyte maturation defect 9

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.10

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.14

REVEL

Benign

0.17

Sift

Benign

0.36

Sift4G

Benign

0.38

Polyphen

0.016

Vest4

0.10

MutPred

0.29

Gain of MoRF binding (P = 0.0492);

MVP

0.42

MPC

0.72

ClinPred

0.037

GERP RS

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.085

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.58

Position offset: -5

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over