rs2305120

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005762.3(TRIM28):c.1170G>A(p.Lys390Lys) 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:4

Conservation

PhyloP100: 0.126

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

childhood kidney Wilms tumor
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
kidney Wilms tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRIM28 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TRIM28	NM_005762.3 link	c.1170G>A	p.Lys390Lys	synonymous_variant	Exon 8 of 17	ENST00000253024.10	NP_005753.1	Q13263-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM28	ENST00000253024.10 link	c.1170G>A	p.Lys390Lys	synonymous_variant	Exon 8 of 17	1	NM_005762.3	ENSP00000253024.4		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

GnomAD2 exomes

AF:

0.105

AC:

26436

AN:

251398

AF XY:

0.104

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 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

African (AFR)

AF:

0.0799

AC:

2675

AN:

33480

American (AMR)

AF:

0.116

AC:

5182

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

1588

AN:

26136

East Asian (EAS)

AF:

0.317

AC:

12573

AN:

39698

South Asian (SAS)

AF:

0.136

AC:

11762

AN:

86256

European-Finnish (FIN)

AF:

0.0850

AC:

4538

AN:

53388

Middle Eastern (MID)

AF:

0.0537

AC:

310

AN:

5768

European-Non Finnish (NFE)

AF:

0.0644

AC:

71623

AN:

1111984

Other (OTH)

AF:

0.0888

AC:

5365

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6488

12975

19463

25950

32438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2938

5876

8814

11752

14690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0845

AC:

12872

AN:

152242

Hom.:

704

Cov.:

AF XY:

0.0865

AC XY:

6440

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0858

AC:

3565

AN:

41542

American (AMR)

AF:

0.0850

AC:

1300

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

205

AN:

3472

East Asian (EAS)

AF:

0.323

AC:

1675

AN:

5180

South Asian (SAS)

AF:

0.151

AC:

728

AN:

4828

European-Finnish (FIN)

AF:

0.0801

AC:

849

AN:

10598

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0635

AC:

4318

AN:

68012

Other (OTH)

AF:

0.0861

AC:

182

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

591

1182

1774

2365

2956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0741

Hom.:

494

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 05, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

TRIM28-related disorder

Benign:1

Dec 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.82

PhyloP100

0.13

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over