14-91968613-G-A

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.*1060C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 220,372 control chromosomes in the GnomAD database, including 45,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (33526 hom., cov: 32)
  • Exomes 𝑓: 0.58 (11896 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.33

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=-1.01).
• BP6: Variant 14-91968613-G-A is Benign according to our data. Variant chr14-91968613-G-A is described in ClinVar as [Benign]. Clinvar id is 314901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP11	NM_004239.4	c.*1060C>T		3_prime_UTR_variant	21/21	ENST00000267622.8
TRIP11	NM_001321851.1	c.*1060C>T		3_prime_UTR_variant	21/21
TRIP11	XM_047431935.1	c.*1060C>T		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP11	ENST00000267622.8	c.*1060C>T		3_prime_UTR_variant	21/21	1	NM_004239.4	P1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97846 AN: 151914 Hom.: 33466 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.582 AC: 39797 AN: 68340 Hom.: 11896 Cov.: 0 AF XY: 0.583 AC XY: 18411 AN XY: 31602

Gnomad4 AFR exome AF: 0.883

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.593

GnomAD4 genome AF: 0.644 AC: 97964 AN: 152032 Hom.: 33526 Cov.: 32 AF XY: 0.637 AC XY: 47340 AN XY: 74306

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.615

Alfa AF: 0.573 Hom.: 26139

Bravo AF: 0.647

Asia WGS AF: 0.595 AC: 2069 AN: 3478

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	-1.0
Cadd	Benign	0.10
Dann	Benign	0.47

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: rs10142576; hg19: chr14-92434957;