14-91974722-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004239.4(TRIP11):c.5479G>A(p.Gly1827Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,608,338 control chromosomes in the GnomAD database, including 84,925 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1827C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.29 ( 6644 hom., cov: 30)

Exomes 𝑓: 0.32 ( 78281 hom. )

Consequence

TRIP11
NM_004239.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.31

Publications

54 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, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Laboratory for Molecular Medicine
TRIP11-related skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics

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=0.0029513836).

BP6

Variant 14-91974722-C-T is Benign according to our data. Variant chr14-91974722-C-T is described in ClinVar as Benign. ClinVar VariationId is 194954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP11	NM_004239.4 link	c.5479G>A	p.Gly1827Ser	missense_variant	Exon 19 of 21	ENST00000267622.8	NP_004230.2	Q15643-1
TRIP11	NM_001321851.1 link	c.5476G>A	p.Gly1826Ser	missense_variant	Exon 19 of 21		NP_001308780.1
TRIP11	XM_047431935.1 link	c.4153G>A	p.Gly1385Ser	missense_variant	Exon 11 of 13		XP_047287891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622.8 link	c.5479G>A	p.Gly1827Ser	missense_variant	Exon 19 of 21	1	NM_004239.4	ENSP00000267622.4		Q15643-1
TRIP11	ENST00000554357.5 link	c.4624G>A	p.Gly1542Ser	missense_variant	Exon 13 of 15	1		ENSP00000451032.1		H0YJ97

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44103

AN:

151466

Hom.:

6645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.343

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.289

GnomAD2 exomes

AF:

0.306

AC:

76643

AN:

250288

AF XY:

0.316

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.325

AC:

473068

AN:

1456758

Hom.:

78281

Cov.:

AF XY:

0.326

AC XY:

236642

AN XY:

724834

show subpopulations

African (AFR)

AF:

0.225

AC:

7514

AN:

33414

American (AMR)

AF:

0.188

AC:

8392

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

10288

AN:

26082

East Asian (EAS)

AF:

0.375

AC:

14855

AN:

39600

South Asian (SAS)

AF:

0.345

AC:

29725

AN:

86080

European-Finnish (FIN)

AF:

0.325

AC:

17321

AN:

53326

Middle Eastern (MID)

AF:

0.323

AC:

1757

AN:

5436

European-Non Finnish (NFE)

AF:

0.328

AC:

363869

AN:

1107958

Other (OTH)

AF:

0.321

AC:

19347

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

15511

31022

46534

62045

77556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11768

23536

35304

47072

58840

<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:

0.291

AC:

44111

AN:

151580

Hom.:

6644

Cov.:

AF XY:

0.291

AC XY:

21522

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.227

AC:

9374

AN:

41310

American (AMR)

AF:

0.214

AC:

3256

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1349

AN:

3468

East Asian (EAS)

AF:

0.336

AC:

1733

AN:

5154

South Asian (SAS)

AF:

0.339

AC:

1626

AN:

4796

European-Finnish (FIN)

AF:

0.341

AC:

3556

AN:

10420

Middle Eastern (MID)

AF:

0.345

AC:

100

AN:

290

European-Non Finnish (NFE)

AF:

0.327

AC:

22226

AN:

67896

Other (OTH)

AF:

0.286

AC:

605

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1565

3130

4695

6260

7825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.312

Hom.:

28961

Bravo

AF:

0.278

TwinsUK

AF:

0.330

AC:

1223

ALSPAC

AF:

0.334

AC:

1287

ESP6500AA

AF:

0.223

AC:

983

ESP6500EA

AF:

0.329

AC:

2832

ExAC

AF:

0.309

AC:

37520

Asia WGS

AF:

0.305

AC:

1059

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Achondrogenesis, type IA

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 17, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 14, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Odontochondrodysplasia 1

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

2.3

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.11

Sift

Benign

0.045

Sift4G

Benign

0.092

Polyphen

0.90

Vest4

0.062

MPC

0.16

ClinPred

0.027

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.19

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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