rs3742719

Positions:

chr14-91969832-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004239.4(TRIP11):c.5781G>A(p.Ser1927Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,614,112 control chromosomes in the GnomAD database, including 719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 53 hom., cov: 32)

Exomes 𝑓: 0.021 ( 666 hom. )

Consequence

TRIP11
NM_004239.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.857

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 14-91969832-C-T is Benign according to our data. Variant chr14-91969832-C-T is described in ClinVar as [Benign]. Clinvar id is 314927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.857 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP11	NM_004239.4 linkuse as main transcript	c.5781G>A	p.Ser1927Ser	synonymous_variant	21/21	ENST00000267622.8	NP_004230.2	Q15643-1
TRIP11	NM_001321851.1 linkuse as main transcript	c.5778G>A	p.Ser1926Ser	synonymous_variant	21/21		NP_001308780.1
TRIP11	XM_047431935.1 linkuse as main transcript	c.4455G>A	p.Ser1485Ser	synonymous_variant	13/13		XP_047287891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622.8 linkuse as main transcript	c.5781G>A	p.Ser1927Ser	synonymous_variant	21/21	1	NM_004239.4	ENSP00000267622.4		Q15643-1
TRIP11	ENST00000554357.5 linkuse as main transcript	c.4926G>A	p.Ser1642Ser	synonymous_variant	15/15	1		ENSP00000451032.1		H0YJ97

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2823

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.0655

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.0267

AC:

6700

AN:

250738

Hom.:

197

AF XY:

0.0286

AC XY:

3883

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00627

Gnomad ASJ exome

AF:

0.0245

Gnomad EAS exome

AF:

0.0604

Gnomad SAS exome

AF:

0.0656

Gnomad FIN exome

AF:

0.0347

Gnomad NFE exome

AF:

0.0191

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0212

AC:

31003

AN:

1461872

Hom.:

666

Cov.:

AF XY:

0.0225

AC XY:

16330

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00666

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.0905

Gnomad4 SAS exome

AF:

0.0628

Gnomad4 FIN exome

AF:

0.0341

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0185

AC:

2823

AN:

152240

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1500

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0274

Gnomad4 EAS

AF:

0.0651

Gnomad4 SAS

AF:

0.0822

Gnomad4 FIN

AF:

0.0311

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0177

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.0700

AC:

243

AN:

3478

EpiCase

AF:

0.0175

EpiControl

AF:

0.0178

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 28, 2023	- -

Achondrogenesis, type IA

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2016

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. -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.96

DANN

Benign

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over