Genetic Variant NM_003302.3:c.688G>A (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:

Genome browser will be placed here

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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