NM_004239.4:c.*952A>T

Variant names:

• chr14-91968721-T-A
• rs1133441
• NM_004239.4:c.*952A>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.*952A>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 0.304 in 227,620 control chromosomes in the GnomAD database, including 10,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6704 hom., cov: 32)
  • Exomes 𝑓: 0.33 (4246 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.107
• Publications: 7 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: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• TRIP11-related skeletal dysplasia

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-91968721-T-A is Benign according to our data. Variant chr14-91968721-T-A is described in ClinVar as Benign. ClinVar VariationId is 314902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 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.*952A>T		3_prime_UTR	Exon 21 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.*952A>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.*952A>T		3_prime_UTR	Exon 21 of 21	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000913145.1		c.*952A>T		3_prime_UTR	Exon 21 of 21	ENSP00000583204.1
	TRIP11	ENST00000876362.1		c.*952A>T		3_prime_UTR	Exon 20 of 20	ENSP00000546421.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44326 AN: 151956 Hom.: 6705 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.329 AC: 24888 AN: 75546 Hom.: 4246 Cov.: 0 AF XY: 0.335 AC XY: 11673 AN XY: 34880

African (AFR) AF: 0.225 AC: 791 AN: 3512

American (AMR) AF: 0.214 AC: 490 AN: 2292

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1843 AN: 4724

East Asian (EAS) AF: 0.409 AC: 4293 AN: 10504

South Asian (SAS) AF: 0.320 AC: 204 AN: 638

European-Finnish (FIN) AF: 0.324 AC: 400 AN: 1234

Middle Eastern (MID) AF: 0.358 AC: 166 AN: 464

European-Non Finnish (NFE) AF: 0.322 AC: 14826 AN: 45980

Other (OTH) AF: 0.303 AC: 1875 AN: 6198

GnomAD4 genome AF: 0.292 AC: 44332 AN: 152074 Hom.: 6704 Cov.: 32 AF XY: 0.291 AC XY: 21623 AN XY: 74330

African (AFR) AF: 0.226 AC: 9382 AN: 41486

American (AMR) AF: 0.213 AC: 3260 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1352 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1747 AN: 5172

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4818

European-Finnish (FIN) AF: 0.340 AC: 3594 AN: 10572

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22368 AN: 67964

Other (OTH) AF: 0.288 AC: 607 AN: 2110

Alfa AF: 0.127 Hom.: 226

Bravo AF: 0.279

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.80
CADD	Benign	3.6
DANN	Benign	0.81
PhyloP100		0.11
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: rs1133441; hg19: chr14-92435065;