rs143524436

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004239.4(TRIP11):c.2134G>A(p.Glu712Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00886 in 1,614,040 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 89 hom. )

Consequence

TRIP11
NM_004239.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 4.85

Publications

19 publications found

Variant links:

Genes affected

TRIP11 (HGNC:12305): (thyroid hormone receptor interactor 11) This gene was identified based on the interaction of its protein product with thyroid hormone receptor beta. This protein is associated with the Golgi apparatus. The N-terminal region of the protein binds Golgi membranes and the C-terminal region binds the minus ends of microtubules; thus, the protein is thought to play a role in assembly and maintenance of the Golgi ribbon structure around the centrosome. Mutations in this gene cause achondrogenesis type IA.[provided by RefSeq, Mar 2010]

TRIP11 Gene-Disease associations (from GenCC):

achondrogenesis type IA
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet
TRIP11-related skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen

TRIP11 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=0.0049014688).

BP6

Variant 14-92005842-C-T is Benign according to our data. Variant chr14-92005842-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 314964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00802 (1221/152308) while in subpopulation NFE AF = 0.0103 (700/68026). AF 95% confidence interval is 0.00966. There are 10 homozygotes in GnomAd4. There are 643 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	NM_004239.4	MANE Select	c.2134G>A	p.Glu712Lys	missense	Exon 11 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.2131G>A	p.Glu711Lys	missense	Exon 11 of 21	NP_001308780.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIP11	ENST00000267622.8	TSL:1 MANE Select	c.2134G>A	p.Glu712Lys	missense	Exon 11 of 21	ENSP00000267622.4	Q15643-1
TRIP11	ENST00000554357.5	TSL:1	c.1279G>A	p.Glu427Lys	missense	Exon 5 of 15	ENSP00000451032.1	H0YJ97
TRIP11	ENST00000913145.1		c.2131G>A	p.Glu711Lys	missense	Exon 11 of 21	ENSP00000583204.1

Frequencies

GnomAD3 genomes

AF:

0.00803

AC:

1222

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00764

AC:

1915

AN:

250718

AF XY:

0.00765

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.00905

Gnomad OTH exome

AF:

0.00964

GnomAD4 exome

AF:

0.00894

AC:

13073

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00879

AC XY:

6392

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33474

American (AMR)

AF:

0.00418

AC:

187

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39664

South Asian (SAS)

AF:

0.00299

AC:

258

AN:

86254

European-Finnish (FIN)

AF:

0.0308

AC:

1644

AN:

53346

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00938

AC:

10432

AN:

1111986

Other (OTH)

AF:

0.00800

AC:

483

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

887

1773

2660

3546

4433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.00802

AC:

1221

AN:

152308

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

643

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41564

American (AMR)

AF:

0.00634

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0301

AC:

320

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

700

AN:

68026

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00835

Hom.:

Bravo

AF:

0.00592

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00965

AC:

ExAC

AF:

0.00741

AC:

899

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.00976

EpiControl

AF:

0.0100

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

Achondrogenesis, type IA (2)

not specified (2)

Achondrogenesis, type IA;C5542277:Odontochondrodysplasia 1 (1)

Connective tissue disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

0.14

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.8

PhyloP100

4.8

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.2

REVEL

Benign

0.10

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.026

Polyphen

0.98

Vest4

0.19

MVP

0.45

MPC

0.24

ClinPred

0.020

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.34

Mutation Taster

=95/5

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over