14-91968613-G-A

Variant names:

• chr14-91968613-G-A
• rs10142576
• NM_004239.4:c.*1060C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.33
• Publications: 6 publications found

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]

TRIP11 Gene-Disease associations (from GenCC):

• achondrogenesis type IA

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet
• TRIP11-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 314901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	NM_004239.4	MANE Select	c.*1060C>T		3_prime_UTR	Exon 21 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.*1060C>T		3_prime_UTR	Exon 21 of 21	NP_001308780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	ENST00000267622.8	TSL:1 MANE Select	c.*1060C>T		3_prime_UTR	Exon 21 of 21	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000913145.1		c.*1060C>T		3_prime_UTR	Exon 21 of 21	ENSP00000583204.1
	TRIP11	ENST00000876362.1		c.*1060C>T		3_prime_UTR	Exon 20 of 20	ENSP00000546421.1

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

African (AFR) AF: 0.883 AC: 2709 AN: 3068

American (AMR) AF: 0.456 AC: 915 AN: 2006

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2609 AN: 4222

East Asian (EAS) AF: 0.566 AC: 5517 AN: 9748

South Asian (SAS) AF: 0.611 AC: 352 AN: 576

European-Finnish (FIN) AF: 0.544 AC: 621 AN: 1142

Middle Eastern (MID) AF: 0.589 AC: 259 AN: 440

European-Non Finnish (NFE) AF: 0.566 AC: 23480 AN: 41514

Other (OTH) AF: 0.593 AC: 3335 AN: 5624

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

African (AFR) AF: 0.887 AC: 36830 AN: 41516

American (AMR) AF: 0.496 AC: 7570 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2128 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2359 AN: 5172

South Asian (SAS) AF: 0.608 AC: 2925 AN: 4812

European-Finnish (FIN) AF: 0.539 AC: 5689 AN: 10550

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38478 AN: 67930

Other (OTH) AF: 0.615 AC: 1297 AN: 2108

Alfa AF: 0.584 Hom.: 35305

Bravo AF: 0.647

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Achondrogenesis, type IA (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.47
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10142576; hg19: chr14-92434957;