Genetic Variant ENST00000596758.5:c.1738T>G (chr19-6751282-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000596758.5(TRIP10):c.1738T>G(p.Cys580Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,608,724 control chromosomes in the GnomAD database, including 29,568 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3871 hom., cov: 32)

Exomes 𝑓: 0.19 ( 25697 hom. )

Consequence

TRIP10
ENST00000596758.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.236

Publications

36 publications found

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:

ENSG00000269680 (HGNC:58603):

ENSG00000269680 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013584793).

BP6

Variant 19-6751282-T-G is Benign according to our data. Variant chr19-6751282-T-G is described in ClinVar as Benign. ClinVar VariationId is 403569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP10	NM_001288962.2 link	c.*71T>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000313244.14	NP_001275891.1	Q15642-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP10	ENST00000313244.14 link	c.*71T>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_001288962.2	ENSP00000320117.7		Q15642-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33426

AN:

151888

Hom.:

3855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.207

GnomAD2 exomes

AF:

0.204

AC:

49716

AN:

243922

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.185

AC:

269531

AN:

1456718

Hom.:

25697

Cov.:

AF XY:

0.183

AC XY:

132269

AN XY:

724440

show subpopulations

African (AFR)

AF:

0.290

AC:

9665

AN:

33364

American (AMR)

AF:

0.245

AC:

10872

AN:

44346

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

4270

AN:

25964

East Asian (EAS)

AF:

0.239

AC:

9447

AN:

39468

South Asian (SAS)

AF:

0.135

AC:

11607

AN:

85722

European-Finnish (FIN)

AF:

0.240

AC:

12585

AN:

52412

Middle Eastern (MID)

AF:

0.201

AC:

1158

AN:

5754

European-Non Finnish (NFE)

AF:

0.178

AC:

198020

AN:

1109496

Other (OTH)

AF:

0.198

AC:

11907

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

12224

24449

36673

48898

61122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7030

14060

21090

28120

35150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33485

AN:

152006

Hom.:

3871

Cov.:

AF XY:

0.222

AC XY:

16467

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.285

AC:

11790

AN:

41404

American (AMR)

AF:

0.235

AC:

3590

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

527

AN:

3470

East Asian (EAS)

AF:

0.275

AC:

1417

AN:

5162

South Asian (SAS)

AF:

0.133

AC:

642

AN:

4822

European-Finnish (FIN)

AF:

0.250

AC:

2640

AN:

10574

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12310

AN:

67976

Other (OTH)

AF:

0.212

AC:

448

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1312

2624

3936

5248

6560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

7572

Bravo

AF:

0.225

TwinsUK

AF:

0.170

AC:

629

ALSPAC

AF:

0.177

AC:

683

ExAC

AF:

0.201

AC:

24325

Asia WGS

AF:

0.245

AC:

852

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.188

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

PhyloP100

0.24

Vest4

0.25

ClinPred

0.00091

GERP RS

1.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over