Variant chr2-229767552-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001348323.3(TRIP12):c.*2C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.139 in 1,603,182 control chromosomes in the GnomAD database, including 16,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1906 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14381 hom. )

Consequence

TRIP12
NM_001348323.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.66

Variant links:

Genes affected

TRIP12 (HGNC:12306): (thyroid hormone receptor interactor 12) The protein encoded by this gene is an E3 ubiquitin-protein ligase involved in the degradation of the p19ARF/ARF isoform of CDKN2A, a tumor suppressor. The encoded protein also plays a role in the DNA damage response by regulating the stability of USP7, which regulates tumor suppressor p53. [provided by RefSeq, Jan 2017]

TRIP12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 2-229767552-G-A is Benign according to our data. Variant chr2-229767552-G-A is described in ClinVar as [Benign]. Clinvar id is 1181222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP12	NM_001348323.3 linkuse as main transcript	c.*2C>T		3_prime_UTR_variant	42/42	ENST00000675903.1	NP_001335252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP12	ENST00000675903 linkuse as main transcript	c.*2C>T		3_prime_UTR_variant	42/42		NM_001348323.3	ENSP00000502713.1		A0A6Q8PHK0

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23221

AN:

152120

Hom.:

1905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0928

Gnomad SAS

AF:

0.0992

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.140

AC:

34111

AN:

243326

Hom.:

2684

AF XY:

0.134

AC XY:

17613

AN XY:

131298

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.0947

Gnomad SAS exome

AF:

0.0976

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.137

AC:

199143

AN:

1450944

Hom.:

14381

Cov.:

AF XY:

0.135

AC XY:

97265

AN XY:

720920

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.0807

Gnomad4 SAS exome

AF:

0.0994

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.153

AC:

23243

AN:

152238

Hom.:

1906

Cov.:

AF XY:

0.151

AC XY:

11207

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0932

Gnomad4 SAS

AF:

0.0995

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.131

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.137

Hom.:

2447

Bravo

AF:

0.166

Asia WGS

AF:

0.113

AC:

396

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

TRIP12-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.89

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over