14-91968333-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004239.4(TRIP11):c.*1339_*1340insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 197,954 control chromosomes in the GnomAD database, including 133 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (131 hom., cov: 31)
  • Exomes 𝑓: 0.012 (2 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B: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 Benign. Variant got -10 ACMG points.

• BP6: Variant 14-91968333-A-AT is Benign according to our data. Variant chr14-91968333-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 314897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP11	NM_004239.4	c.*1339_*1340insA		3_prime_UTR_variant	21/21	ENST00000267622.8
TRIP11	NM_001321851.1	c.*1339_*1340insA		3_prime_UTR_variant	21/21
TRIP11	XM_047431935.1	c.*1339_*1340insA		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP11	ENST00000267622.8	c.*1339_*1340insA		3_prime_UTR_variant	21/21	1	NM_004239.4	P1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3557 AN: 150254 Hom.: 128 Cov.: 31

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000816

Gnomad OTH AF: 0.0194

GnomAD4 exome AF: 0.0115 AC: 549 AN: 47590 Hom.: 2 Cov.: 0 AF XY: 0.0111 AC XY: 244 AN XY: 21960

Gnomad4 AFR exome AF: 0.0678

Gnomad4 AMR exome AF: 0.00729

Gnomad4 ASJ exome AF: 0.00500

Gnomad4 EAS exome AF: 0.0138

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00658

Gnomad4 OTH exome AF: 0.0176

GnomAD4 genome AF: 0.0239 AC: 3588 AN: 150364 Hom.: 131 Cov.: 31 AF XY: 0.0238 AC XY: 1746 AN XY: 73418

Gnomad4 AFR AF: 0.0736

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000816

Gnomad4 OTH AF: 0.0221

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Achondrogenesis Benign:1

Likely benign, 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;