2-229767552-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.66

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]

ACMG classification

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	UniProt
TRIP12	NM_001348323.3	c.*2C>T		3_prime_UTR_variant	42/42	ENST00000675903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP12	ENST00000675903.1	c.*2C>T		3_prime_UTR_variant	42/42		NM_001348323.3	P3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23221 AN: 152120 Hom.: 1905 Cov.: 33

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

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.: 31 AF XY: 0.135 AC XY: 97265 AN XY: 720920

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.: 33 AF XY: 0.151 AC XY: 11207 AN XY: 74446

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

TRIP12-related disorder Benign:1

Benign, criteria provided, single submitter

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	13
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

Other links and lift over

dbSNP: rs6687; hg19: chr2-230632268; COSMIC: COSV52259360; COSMIC: COSV52259360;