Variant chr19-6743554-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001288962.2(TRIP10):c.469C>T(p.Arg157Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,580,516 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: 𝑓 0.00010 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

TRIP10
NM_001288962.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.963

Variant links:

Genes affected

TRIP10 (HGNC:12304): (thyroid hormone receptor interactor 10) Enables identical protein binding activity. Predicted to be involved in actin cytoskeleton organization; endocytosis; and signal transduction. Located in nucleoplasm. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRIP10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38691655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP10	NM_001288962.2 linkuse as main transcript	c.469C>T	p.Arg157Trp	missense_variant	6/15	ENST00000313244.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP10	ENST00000313244.14 linkuse as main transcript	c.469C>T	p.Arg157Trp	missense_variant	6/15	1	NM_001288962.2	P3	Q15642-1

Frequencies

GnomAD3 genomes

AF:

0.000100

AC:

AN:

139854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000266

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:

0.000196

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

250856

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000578

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:

0.0000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

183

AN:

1440592

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

716444

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.000100

AC:

AN:

139924

Hom.:

Cov.:

AF XY:

0.0000597

AC XY:

AN XY:

67014

show subpopulations

Gnomad4 AFR

AF:

0.0000265

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:

0.000196

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.469C>T (p.R157W) alteration is located in exon 6 (coding exon 6) of the TRIP10 gene. This alteration results from a C to T substitution at nucleotide position 469, causing the arginine (R) at amino acid position 157 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;D;T;.

Eigen

Benign

-0.029

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.68

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.8

.;L;L;.;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-5.7

.;D;D;.;.

REVEL

Benign

0.19

Sift

Pathogenic

0.0

.;D;D;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.;.

Vest4

0.47

MVP

0.72

MPC

0.66

ClinPred

0.68

GERP RS

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.47

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over