14-91968924-C-T

Variant names:

• chr14-91968924-C-T
• rs150189603
• NM_004239.4:c.*749G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004239.4(TRIP11):​c.*749G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 231,606 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 14-91968924-C-T is Benign according to our data. Variant chr14-91968924-C-T is described in ClinVar as Benign. ClinVar VariationId is 884357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00678 (1032/152164) while in subpopulation AFR AF = 0.0233 (966/41510). AF 95% confidence interval is 0.0221. There are 11 homozygotes in GnomAd4. There are 495 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.*749G>A		3_prime_UTR	Exon 21 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.*749G>A		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.*749G>A		3_prime_UTR	Exon 21 of 21	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000913145.1		c.*749G>A		3_prime_UTR	Exon 21 of 21	ENSP00000583204.1
	TRIP11	ENST00000876362.1		c.*749G>A		3_prime_UTR	Exon 20 of 20	ENSP00000546421.1

Frequencies

GnomAD3 genomes AF: 0.00677 AC: 1029 AN: 152046 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00719

GnomAD4 exome AF: 0.00149 AC: 118 AN: 79442 Hom.: 3 Cov.: 0 AF XY: 0.00134 AC XY: 49 AN XY: 36624

African (AFR) AF: 0.0218 AC: 82 AN: 3764

American (AMR) AF: 0.00369 AC: 9 AN: 2438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5014

East Asian (EAS) AF: 0.00 AC: 0 AN: 11172

South Asian (SAS) AF: 0.00 AC: 0 AN: 680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 474

European-Non Finnish (NFE) AF: 0.0000615 AC: 3 AN: 48742

Other (OTH) AF: 0.00364 AC: 24 AN: 6602

GnomAD4 genome AF: 0.00678 AC: 1032 AN: 152164 Hom.: 11 Cov.: 32 AF XY: 0.00665 AC XY: 495 AN XY: 74396

African (AFR) AF: 0.0233 AC: 966 AN: 41510

American (AMR) AF: 0.00288 AC: 44 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68008

Other (OTH) AF: 0.00712 AC: 15 AN: 2108

Alfa AF: 0.00410 Hom.: 3

Bravo AF: 0.00795

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Achondrogenesis, type IA (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.74
DANN	Benign	0.42
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism

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: rs150189603; hg19: chr14-92435268;