dbSNP rs1049229: TRIP10:p.Glu575Gly (chr19-6751268-A-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.1724A>G(p.Glu575Gly) 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 1,611,418 control chromosomes in the GnomAD database, including 29,491 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 ( 3800 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25691 hom. )

Consequence

TRIP10
ENST00000596758.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.337

Publications

21 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=0.001078546).

BP6

Variant 19-6751268-A-G is Benign according to our data. Variant chr19-6751268-A-G is described in ClinVar as Benign. ClinVar VariationId is 403567.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.*57A>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.*57A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_001288962.2	ENSP00000320117.7		Q15642-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33261

AN:

151622

Hom.:

3784

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:

0.275

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.203

AC:

50150

AN:

247002

AF XY:

0.196

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.245

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:

0.208

GnomAD4 exome

AF:

0.185

AC:

269860

AN:

1459680

Hom.:

25691

Cov.:

AF XY:

0.182

AC XY:

132471

AN XY:

726154

show subpopulations

African (AFR)

AF:

0.289

AC:

9667

AN:

33432

American (AMR)

AF:

0.244

AC:

10881

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

4289

AN:

26088

East Asian (EAS)

AF:

0.239

AC:

9465

AN:

39612

South Asian (SAS)

AF:

0.137

AC:

11780

AN:

86056

European-Finnish (FIN)

AF:

0.240

AC:

12655

AN:

52662

Middle Eastern (MID)

AF:

0.199

AC:

1146

AN:

5758

European-Non Finnish (NFE)

AF:

0.178

AC:

198074

AN:

1111204

Other (OTH)

AF:

0.197

AC:

11903

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

12451

24901

37352

49802

62253

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:

33320

AN:

151738

Hom.:

3800

Cov.:

AF XY:

0.221

AC XY:

16380

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.284

AC:

11721

AN:

41320

American (AMR)

AF:

0.233

AC:

3553

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

527

AN:

3470

East Asian (EAS)

AF:

0.275

AC:

1407

AN:

5124

South Asian (SAS)

AF:

0.135

AC:

650

AN:

4802

European-Finnish (FIN)

AF:

0.249

AC:

2612

AN:

10508

Middle Eastern (MID)

AF:

0.212

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12286

AN:

67926

Other (OTH)

AF:

0.210

AC:

444

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1309

2618

3928

5237

6546

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:

0.197

Hom.:

1706

Bravo

AF:

0.225

TwinsUK

AF:

0.169

AC:

627

ALSPAC

AF:

0.177

AC:

683

ExAC

AF:

0.201

AC:

24364

Asia WGS

AF:

0.245

AC:

852

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

0.055

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.0

PhyloP100

0.34

Vest4

0.11

ClinPred

0.00086

GERP RS

1.0

Mutation Taster

=94/6

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