Genetic Variant ENST00000596758.5:c.1726C>T (chr19-6751270-C-T) – 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.1726C>T(p.Pro576Ser) 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 1,611,074 control chromosomes in the GnomAD database, including 29,470 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 ( 3795 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25675 hom. )

Consequence

TRIP10
ENST00000596758.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.70

Publications

32 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=0.0015844703).

BP6

Variant 19-6751270-C-T is Benign according to our data. Variant chr19-6751270-C-T is described in ClinVar as Benign. ClinVar VariationId is 403568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP10	NM_001288962.2 link	c.*59C>T		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.*59C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_001288962.2	ENSP00000320117.7		Q15642-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33240

AN:

151718

Hom.:

3779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.203

AC:

50086

AN:

246766

AF XY:

0.196

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.246

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.185

AC:

269661

AN:

1459238

Hom.:

25675

Cov.:

AF XY:

0.182

AC XY:

132321

AN XY:

725900

show subpopulations

African (AFR)

AF:

0.289

AC:

9669

AN:

33434

American (AMR)

AF:

0.244

AC:

10881

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4289

AN:

26058

East Asian (EAS)

AF:

0.239

AC:

9470

AN:

39590

South Asian (SAS)

AF:

0.135

AC:

11600

AN:

86000

European-Finnish (FIN)

AF:

0.240

AC:

12642

AN:

52642

Middle Eastern (MID)

AF:

0.199

AC:

1145

AN:

5754

European-Non Finnish (NFE)

AF:

0.178

AC:

198070

AN:

1110942

Other (OTH)

AF:

0.197

AC:

11895

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

12528

25057

37585

50114

62642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7028

14056

21084

28112

35140

<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:

0.219

AC:

33299

AN:

151836

Hom.:

3795

Cov.:

AF XY:

0.221

AC XY:

16368

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.283

AC:

11715

AN:

41346

American (AMR)

AF:

0.232

AC:

3550

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

527

AN:

3472

East Asian (EAS)

AF:

0.274

AC:

1406

AN:

5140

South Asian (SAS)

AF:

0.133

AC:

640

AN:

4810

European-Finnish (FIN)

AF:

0.248

AC:

2612

AN:

10530

Middle Eastern (MID)

AF:

0.212

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12285

AN:

67950

Other (OTH)

AF:

0.210

AC:

444

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1278

2555

3833

5110

6388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.195

Hom.:

1731

Bravo

AF:

0.225

TwinsUK

AF:

0.169

AC:

627

ALSPAC

AF:

0.177

AC:

682

ExAC

AF:

0.201

AC:

24326

Asia WGS

AF:

0.245

AC:

850

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.187

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

0.081

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.98

PhyloP100

1.7

Vest4

0.37

ClinPred

0.00044

GERP RS

-0.062

Mutation Taster

=98/2

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