14-91968299-T-G

Position:

• chr14-91968299-T-G

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.*1374A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 204,686 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (52 hom., cov: 32)
  • Exomes 𝑓: 0.031 (51 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0520

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=-0.48).
• BP6: Variant 14-91968299-T-G is Benign according to our data. Variant chr14-91968299-T-G is described in ClinVar as [Benign]. Clinvar id is 314896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP11	NM_004239.4	c.*1374A>C		3_prime_UTR_variant	21/21	ENST00000267622.8	NP_004230.2
TRIP11	NM_001321851.1	c.*1374A>C		3_prime_UTR_variant	21/21		NP_001308780.1
TRIP11	XM_047431935.1	c.*1374A>C		3_prime_UTR_variant	13/13		XP_047287891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622	c.*1374A>C		3_prime_UTR_variant	21/21	1	NM_004239.4	ENSP00000267622.4

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2857 AN: 152226 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0306 AC: 1603 AN: 52342 Hom.: 51 Cov.: 0 AF XY: 0.0314 AC XY: 763 AN XY: 24264

Gnomad4 AFR exome AF: 0.00314

Gnomad4 AMR exome AF: 0.00800

Gnomad4 ASJ exome AF: 0.0331

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0786

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.0165

Gnomad4 OTH exome AF: 0.0173

GnomAD4 genome AF: 0.0188 AC: 2858 AN: 152344 Hom.: 52 Cov.: 32 AF XY: 0.0204 AC XY: 1522 AN XY: 74486

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0140 Hom.: 6

Bravo AF: 0.0147

Asia WGS AF: 0.0710 AC: 245 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 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	-0.48
CADD	Benign	7.6
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: rs74801826; hg19: chr14-92434643;