rs3742719

Variant names:

• chr14-91969832-C-T
• rs3742719
• NM_004239.4:c.5781G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004239.4(TRIP11):​c.5781G>A​(p.Ser1927Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,614,112 control chromosomes in the GnomAD database, including 719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (53 hom., cov: 32)
  • Exomes 𝑓: 0.021 (666 hom.)
• Consequence: TRIP11 NM_004239.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.857
• 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, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Laboratory for Molecular Medicine
• TRIP11-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.015).
• BP6: Variant 14-91969832-C-T is Benign according to our data. Variant chr14-91969832-C-T is described in ClinVar as Benign. ClinVar VariationId is 314927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.857 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP11	NM_004239.4	c.5781G>A	p.Ser1927Ser	synonymous_variant	Exon 21 of 21	ENST00000267622.8	NP_004230.2
TRIP11	NM_001321851.1	c.5778G>A	p.Ser1926Ser	synonymous_variant	Exon 21 of 21		NP_001308780.1
TRIP11	XM_047431935.1	c.4455G>A	p.Ser1485Ser	synonymous_variant	Exon 13 of 13		XP_047287891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622.8	c.5781G>A	p.Ser1927Ser	synonymous_variant	Exon 21 of 21	1	NM_004239.4	ENSP00000267622.4
TRIP11	ENST00000554357.5	c.4926G>A	p.Ser1642Ser	synonymous_variant	Exon 15 of 15	1		ENSP00000451032.1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2823 AN: 152122 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.0267 AC: 6700 AN: 250738 AF XY: 0.0286

Gnomad AFR exome AF: 0.00283

Gnomad AMR exome AF: 0.00627

Gnomad ASJ exome AF: 0.0245

Gnomad EAS exome AF: 0.0604

Gnomad FIN exome AF: 0.0347

Gnomad NFE exome AF: 0.0191

Gnomad OTH exome AF: 0.0261

GnomAD4 exome AF: 0.0212 AC: 31003 AN: 1461872 Hom.: 666 Cov.: 31 AF XY: 0.0225 AC XY: 16330 AN XY: 727228

African (AFR) AF: 0.00233 AC: 78 AN: 33480

American (AMR) AF: 0.00666 AC: 298 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 648 AN: 26134

East Asian (EAS) AF: 0.0905 AC: 3593 AN: 39700

South Asian (SAS) AF: 0.0628 AC: 5413 AN: 86246

European-Finnish (FIN) AF: 0.0341 AC: 1824 AN: 53420

Middle Eastern (MID) AF: 0.0104 AC: 60 AN: 5766

European-Non Finnish (NFE) AF: 0.0160 AC: 17797 AN: 1112006

Other (OTH) AF: 0.0214 AC: 1292 AN: 60396

GnomAD4 genome AF: 0.0185 AC: 2823 AN: 152240 Hom.: 53 Cov.: 32 AF XY: 0.0202 AC XY: 1500 AN XY: 74418

African (AFR) AF: 0.00344 AC: 143 AN: 41548

American (AMR) AF: 0.0112 AC: 171 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3472

East Asian (EAS) AF: 0.0651 AC: 337 AN: 5176

South Asian (SAS) AF: 0.0822 AC: 396 AN: 4820

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0188 AC: 1280 AN: 68024

Other (OTH) AF: 0.0166 AC: 35 AN: 2106

Alfa AF: 0.0177 Hom.: 17

Bravo AF: 0.0146

Asia WGS AF: 0.0700 AC: 243 AN: 3478

EpiCase AF: 0.0175

EpiControl AF: 0.0178

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Achondrogenesis, type IA Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

Jun 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Connective tissue disorder Benign:1

May 11, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.96
DANN	Benign	0.60
PhyloP100		-0.86
Mutation Taster		=99/1	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: rs3742719; hg19: chr14-92436176;