14-91967929-C-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.*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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

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=-0.9).
• 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP11	NM_004239.4	c.*1744G>A		3_prime_UTR_variant	21/21	ENST00000267622.8
TRIP11	NM_001321851.1	c.*1744G>A		3_prime_UTR_variant	21/21
TRIP11	XM_047431935.1	c.*1744G>A		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP11	ENST00000267622.8	c.*1744G>A		3_prime_UTR_variant	21/21	1	NM_004239.4	P1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5556 AN: 152062 Hom.: 292 Cov.: 32

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.: 16 Cov.: 0 AF XY: 0.00819 AC XY: 184 AN XY: 22458

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.: 32 AF XY: 0.0361 AC XY: 2689 AN XY: 74386

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.: 32

Bravo AF: 0.0412

Asia WGS AF: 0.0670 AC: 231 AN: 3474

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 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

Other links and lift over

dbSNP: rs11848512; hg19: chr14-92434273;