Variant 19-6744921-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001288962.2(TRIP10):c.911C>T(p.Ser304Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,614,178 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

TRIP10
NM_001288962.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05777648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP10	NM_001288962.2 linkuse as main transcript	c.911C>T	p.Ser304Leu	missense_variant	9/15	ENST00000313244.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP10	ENST00000313244.14 linkuse as main transcript	c.911C>T	p.Ser304Leu	missense_variant	9/15	1	NM_001288962.2	P3	Q15642-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

251008

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000698

AC:

102

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000112

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

Dec 14, 2023

The c.911C>T (p.S304L) alteration is located in exon 9 (coding exon 9) of the TRIP10 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the serine (S) at amino acid position 304 to be replaced by a leucine (L). 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

Benign

0.083

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.058

T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.1

.;L;L;.

MutationTaster

Benign

0.94

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.0

.;N;N;.

REVEL

Benign

0.16

Sift

Benign

0.26

.;T;T;.

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.50, 0.0080

.;P;B;.

Vest4

0.33

MVP

0.82

MPC

0.18

ClinPred

0.030

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.093

gMVP

0.51

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