Genetic Variant TRIP6:p.Val230Ile (chr7-100868819-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003302.3(TRIP6):c.688G>A(p.Val230Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,521,606 control chromosomes in the GnomAD database, including 63,192 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5631 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57561 hom. )

Consequence

TRIP6
NM_003302.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

47 publications found

Variant links:

Genes affected

TRIP6 (HGNC:12311): (thyroid hormone receptor interactor 6) This gene is a member of the zyxin family and encodes a protein with three LIM zinc-binding domains. This protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner and it regulates LPA-induced cell migration. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

TRIP6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011588335).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP6	NM_003302.3 link	c.688G>A	p.Val230Ile	missense_variant	Exon 4 of 9	ENST00000200457.9	NP_003293.2	Q15654-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP6	ENST00000200457.9 link	c.688G>A	p.Val230Ile	missense_variant	Exon 4 of 9	1	NM_003302.3	ENSP00000200457.4		Q15654-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38008

AN:

152008

Hom.:

5620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.276

GnomAD2 exomes

AF:

0.299

AC:

50866

AN:

169870

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.284

AC:

388630

AN:

1369480

Hom.:

57561

Cov.:

AF XY:

0.283

AC XY:

190337

AN XY:

673166

show subpopulations

African (AFR)

AF:

0.0972

AC:

2903

AN:

29862

American (AMR)

AF:

0.477

AC:

13560

AN:

28416

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

4867

AN:

20208

East Asian (EAS)

AF:

0.450

AC:

17259

AN:

38320

South Asian (SAS)

AF:

0.268

AC:

19097

AN:

71130

European-Finnish (FIN)

AF:

0.266

AC:

13053

AN:

49062

Middle Eastern (MID)

AF:

0.238

AC:

947

AN:

3984

European-Non Finnish (NFE)

AF:

0.281

AC:

301053

AN:

1072322

Other (OTH)

AF:

0.283

AC:

15891

AN:

56176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

17221

34442

51664

68885

86106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10414

20828

31242

41656

52070

<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:

0.250

AC:

38018

AN:

152126

Hom.:

5631

Cov.:

AF XY:

0.256

AC XY:

19045

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.106

AC:

4420

AN:

41564

American (AMR)

AF:

0.428

AC:

6546

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

874

AN:

3470

East Asian (EAS)

AF:

0.448

AC:

2298

AN:

5134

South Asian (SAS)

AF:

0.266

AC:

1283

AN:

4824

European-Finnish (FIN)

AF:

0.273

AC:

2888

AN:

10584

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18685

AN:

67942

Other (OTH)

AF:

0.277

AC:

585

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1399

2798

4197

5596

6995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.271

Hom.:

15517

Bravo

AF:

0.260

ESP6500AA

AF:

0.112

AC:

414

ESP6500EA

AF:

0.269

AC:

2193

ExAC

AF:

0.285

AC:

33949

Asia WGS

AF:

0.317

AC:

1102

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.5

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.25

REVEL

Benign

0.13

Sift

Benign

0.40

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.016

MPC

0.17

ClinPred

0.015

GERP RS

5.1

PromoterAI

0.21

Neutral

(source)

Varity_R

0.071

gMVP

0.20

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over