14-91968119-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004239.4(TRIP11):c.*1554T>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 0.0195 in 202,524 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (5 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.27

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 14-91968119-A-T is Benign according to our data. Variant chr14-91968119-A-T is described in ClinVar as [Benign]. Clinvar id is 314895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP11	NM_004239.4	c.*1554T>A		3_prime_UTR_variant	21/21	ENST00000267622.8
TRIP11	NM_001321851.1	c.*1554T>A		3_prime_UTR_variant	21/21
TRIP11	XM_047431935.1	c.*1554T>A		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP11	ENST00000267622.8	c.*1554T>A		3_prime_UTR_variant	21/21	1	NM_004239.4	P1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3588 AN: 152224 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.00648 AC: 325 AN: 50182 Hom.: 5 Cov.: 0 AF XY: 0.00624 AC XY: 145 AN XY: 23232

Gnomad4 AFR exome AF: 0.0587

Gnomad4 AMR exome AF: 0.00543

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0114

Gnomad4 SAS exome AF: 0.0419

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0238 AC: 3619 AN: 152342 Hom.: 133 Cov.: 32 AF XY: 0.0236 AC XY: 1759 AN XY: 74498

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.000287 Hom.: 0

Bravo AF: 0.0264

Asia WGS AF: 0.0620 AC: 215 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Achondrogenesis, type IA Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	9.4
Dann	Benign	0.83

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

Other links and lift over

dbSNP: rs11848545; hg19: chr14-92434463;