Genetic Variant TRIP13:p.Val5Met (chr5-893011-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004237.4(TRIP13):c.13G>A(p.Val5Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,413,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIP13
NM_004237.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.19

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:

BRD9 (HGNC:25818): (bromodomain containing 9) Enables lysine-acetylated histone binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

BRD9 links:

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ACMG classification

Classification made for transcript

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=0.19966415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP13	NM_004237.4 link	c.13G>A	p.Val5Met	missense_variant	Exon 1 of 13	ENST00000166345.8	NP_004228.1	Q15645-1
BRD9	NM_023924.5 link	c.-354C>T		upstream_gene_variant		ENST00000467963.6	NP_076413.3	Q9H8M2-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP13	ENST00000166345.8 link	c.13G>A	p.Val5Met	missense_variant	Exon 1 of 13	1	NM_004237.4	ENSP00000166345.3		Q15645-1
BRD9	ENST00000467963.6 link	c.-354C>T		upstream_gene_variant		2	NM_023924.5	ENSP00000419765.1		Q9H8M2-5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149968

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000263

AC:

AN:

189882

Hom.:

AF XY:

0.0000191

AC XY:

AN XY:

104656

show subpopulations

Gnomad AFR exome

AF:

0.000104

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1413424

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

701446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73192

Gnomad4 AFR

AF:

0.00

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:

0.0000151

ExAC

AF:

0.0000253

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.31

MutationAssessor

Benign

-0.34

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.21

REVEL

Benign

0.25

Sift

Benign

0.031

Sift4G

Uncertain

0.043

Polyphen

0.66

Vest4

0.14

MutPred

0.24

Gain of disorder (P = 0.0412);

MVP

0.37

MPC

0.60

ClinPred

0.076

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.097

gMVP

0.18

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