14-91968333-AT-A

Position:

• chr14-91968333-AT-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_004239.4(TRIP11):​c.*1339delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 196,938 control chromosomes in the GnomAD database, including 44 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.013 (39 hom., cov: 31)
  • Exomes 𝑓: 0.011 (5 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00100

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1882/150328) while in subpopulation AFR AF= 0.0417 (1715/41094). AF 95% confidence interval is 0.0401. There are 39 homozygotes in gnomad4. There are 883 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP11	NM_004239.4	c.*1339delA		3_prime_UTR_variant	21/21	ENST00000267622.8	NP_004230.2
TRIP11	NM_001321851.1	c.*1339delA		3_prime_UTR_variant	21/21		NP_001308780.1
TRIP11	XM_047431935.1	c.*1339delA		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.*1339delA		3_prime_UTR_variant	21/21	1	NM_004239.4	ENSP00000267622.4

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1884 AN: 150218 Hom.: 39 Cov.: 31

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00625

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00695

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.00777

GnomAD4 exome AF: 0.0111 AC: 518 AN: 46610 Hom.: 5 Cov.: 0 AF XY: 0.0117 AC XY: 252 AN XY: 21474

Gnomad4 AFR exome AF: 0.0562

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.00810

Gnomad4 EAS exome AF: 0.00584

Gnomad4 SAS exome AF: 0.0148

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00893

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0125 AC: 1882 AN: 150328 Hom.: 39 Cov.: 31 AF XY: 0.0120 AC XY: 883 AN XY: 73396

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.00624

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00654

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000341

Gnomad4 OTH AF: 0.00770

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Achondrogenesis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs35251290; hg19: chr14-92434677;