14-91968488-C-A

Variant names:

• chr14-91968488-C-A
• rs1424828686
• NM_004239.4:c.*1185G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004239.4(TRIP11):​c.*1185G>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 0.00000658 in 152,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.*1185G>T		3_prime_UTR	Exon 21 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.*1185G>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.*1185G>T		3_prime_UTR	Exon 21 of 21	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000913145.1		c.*1185G>T		3_prime_UTR	Exon 21 of 21	ENSP00000583204.1
	TRIP11	ENST00000876362.1		c.*1185G>T		3_prime_UTR	Exon 20 of 20	ENSP00000546421.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 63224 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 29284

African (AFR) AF: 0.00 AC: 0 AN: 2844

American (AMR) AF: 0.00 AC: 0 AN: 1812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4030

East Asian (EAS) AF: 0.00 AC: 0 AN: 9248

South Asian (SAS) AF: 0.00 AC: 0 AN: 544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 386

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 38716

Other (OTH) AF: 0.00 AC: 0 AN: 5266

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74280

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.076

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: rs1424828686; hg19: chr14-92434832;