rs780275994

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004239.4(TRIP11):ā€‹c.4087A>Gā€‹(p.Ile1363Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

TRIP11
NM_004239.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRIP11NM_004239.4 linkuse as main transcriptc.4087A>G p.Ile1363Val missense_variant 11/21 ENST00000267622.8 NP_004230.2 Q15643-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIP11ENST00000267622.8 linkuse as main transcriptc.4087A>G p.Ile1363Val missense_variant 11/211 NM_004239.4 ENSP00000267622.4 Q15643-1
TRIP11ENST00000554357.5 linkuse as main transcriptc.3232A>G p.Ile1078Val missense_variant 5/151 ENSP00000451032.1 H0YJ97

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251140
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461730
Hom.:
0
Cov.:
32
AF XY:
0.00000825
AC XY:
6
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsMar 07, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.043
T
Eigen
Benign
0.063
Eigen_PC
Benign
0.023
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-0.36
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.60
N
REVEL
Benign
0.17
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.042
D
Polyphen
1.0
D
Vest4
0.50
MutPred
0.17
Loss of methylation at K1359 (P = 0.1129);
MVP
0.32
MPC
0.30
ClinPred
0.45
T
GERP RS
5.4
Varity_R
0.11
gMVP
0.17

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780275994; hg19: chr14-92470233; COSMIC: COSV50929385; COSMIC: COSV50929385; API