Variant 14-91967929-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004239.4(TRIP11):c.*1744G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 200,694 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 295 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 16 hom. )

Consequence

TRIP11
NM_004239.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.350

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 14-91967929-C-T is Benign according to our data. Variant chr14-91967929-C-T is described in ClinVar as [Benign]. Clinvar id is 314894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
TRIP11	NM_004239.4 linkuse as main transcript	c.*1744G>A	3_prime_UTR_variant	21/21	ENST00000267622.8	NP_004230.2	Q15643-1
TRIP11	NM_001321851.1 linkuse as main transcript	c.*1744G>A	3_prime_UTR_variant	21/21		NP_001308780.1
TRIP11	XM_047431935.1 linkuse as main transcript	c.*1744G>A	3_prime_UTR_variant	13/13		XP_047287891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622 linkuse as main transcript	c.*1744G>A		3_prime_UTR_variant	21/21	1	NM_004239.4	ENSP00000267622.4		Q15643-1

Frequencies

GnomAD3 genomes

AF:

0.0365

AC:

5556

AN:

152062

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.0376

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.00878

AC:

426

AN:

48514

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

184

AN XY:

22458

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.000321

Gnomad4 EAS exome

AF:

0.0111

Gnomad4 SAS exome

AF:

0.0435

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0367

AC:

5589

AN:

152180

Hom.:

295

Cov.:

AF XY:

0.0361

AC XY:

2689

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0234

Gnomad4 SAS

AF:

0.0372

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0743

Hom.:

Bravo

AF:

0.0412

Asia WGS

AF:

0.0670

AC:

231

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Achondrogenesis, type IA

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.23

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