NM_004239.4:c.201+55C>T

Variant names:

• chr14-92033137-G-A
• rs2273188
• NM_004239.4:c.201+55C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004239.4(TRIP11):​c.201+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 1,319,654 control chromosomes in the GnomAD database, including 505 homozygotes. 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 0.0085 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (444 hom.)
• Consequence: TRIP11 NM_004239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0545 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.201+55C>T		intron	N/A	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.198+55C>T		intron	N/A	NP_001308780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	ENST00000267622.8	TSL:1 MANE Select	c.201+55C>T		intron	N/A	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000555105.1	TSL:1	n.533+55C>T		intron	N/A
	TRIP11	ENST00000913145.1		c.198+55C>T		intron	N/A	ENSP00000583204.1

Frequencies

GnomAD3 genomes AF: 0.00851 AC: 1295 AN: 152096 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00666 AC: 7775 AN: 1167440 Hom.: 444 AF XY: 0.00582 AC XY: 3460 AN XY: 594736

African (AFR) AF: 0.00182 AC: 50 AN: 27540

American (AMR) AF: 0.118 AC: 5178 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.00124 AC: 30 AN: 24212

East Asian (EAS) AF: 0.0461 AC: 1754 AN: 38072

South Asian (SAS) AF: 0.00234 AC: 185 AN: 79176

European-Finnish (FIN) AF: 0.000395 AC: 21 AN: 53198

Middle Eastern (MID) AF: 0.000388 AC: 2 AN: 5156

European-Non Finnish (NFE) AF: 0.000242 AC: 205 AN: 845782

Other (OTH) AF: 0.00692 AC: 350 AN: 50606

GnomAD4 genome AF: 0.00853 AC: 1298 AN: 152214 Hom.: 61 Cov.: 32 AF XY: 0.00962 AC XY: 716 AN XY: 74448

African (AFR) AF: 0.00147 AC: 61 AN: 41538

American (AMR) AF: 0.0576 AC: 880 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.0542 AC: 281 AN: 5182

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4824

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68014

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00413 Hom.: 1

Bravo AF: 0.0149

Asia WGS AF: 0.0300 AC: 105 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.27
PhyloP100		-0.64
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: rs2273188; hg19: chr14-92499481;