Variant rs2305120 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005762.3(TRIM28):c.1170G>A(p.Lys390=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 1,614,062 control chromosomes in the GnomAD database, including 7,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 704 hom., cov: 32)

Exomes 𝑓: 0.079 ( 6380 hom. )

Consequence

TRIM28
NM_005762.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.126

Variant links:

Genes affected

TRIM28 (HGNC:16384): (tripartite motif containing 28) The protein encoded by this gene mediates transcriptional control by interaction with the Kruppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

TRIM28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-58548362-G-A is Benign according to our data. Variant chr19-58548362-G-A is described in ClinVar as [Benign]. Clinvar id is 1262310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.126 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM28	NM_005762.3 linkuse as main transcript	c.1170G>A	p.Lys390=	synonymous_variant	8/17	ENST00000253024.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM28	ENST00000253024.10 linkuse as main transcript	c.1170G>A	p.Lys390=	synonymous_variant	8/17	1	NM_005762.3	P1	Q13263-1

Frequencies

GnomAD3 genomes

AF:

0.0846

AC:

12864

AN:

152124

Hom.:

700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0861

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0851

Gnomad ASJ

AF:

0.0590

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0801

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0635

Gnomad OTH

AF:

0.0793

GnomAD3 exomes

AF:

0.105

AC:

26436

AN:

251398

Hom.:

2058

AF XY:

0.104

AC XY:

14103

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0861

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.0611

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.0818

Gnomad NFE exome

AF:

0.0658

Gnomad OTH exome

AF:

0.0831

GnomAD4 exome

AF:

0.0791

AC:

115616

AN:

1461820

Hom.:

6380

Cov.:

AF XY:

0.0802

AC XY:

58325

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0799

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.0608

Gnomad4 EAS exome

AF:

0.317

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0850

Gnomad4 NFE exome

AF:

0.0644

Gnomad4 OTH exome

AF:

0.0888

GnomAD4 genome

AF:

0.0845

AC:

12872

AN:

152242

Hom.:

704

Cov.:

AF XY:

0.0865

AC XY:

6440

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0858

Gnomad4 AMR

AF:

0.0850

Gnomad4 ASJ

AF:

0.0590

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0801

Gnomad4 NFE

AF:

0.0635

Gnomad4 OTH

AF:

0.0861

Alfa

AF:

0.0701

Hom.:

247

Bravo

AF:

0.0847

Asia WGS

AF:

0.227

AC:

788

AN:

3478

EpiCase

AF:

0.0586

EpiControl

AF:

0.0591

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	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2019	- -

TRIM28-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 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

-0.43

CADD

Benign

7.2

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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