Variant chr19-58544918-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005762.3(TRIM28):c.161G>T(p.Gly54Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,253,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

TRIM28
NM_005762.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24706918).

BS2

High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM28	NM_005762.3 linkuse as main transcript	c.161G>T	p.Gly54Val	missense_variant	1/17	ENST00000253024.10	NP_005753.1	Q13263-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM28	ENST00000253024.10 linkuse as main transcript	c.161G>T	p.Gly54Val	missense_variant	1/17	1	NM_005762.3	ENSP00000253024.4	Q13263-1
TRIM28	ENST00000341753.10 linkuse as main transcript	c.161G>T	p.Gly54Val	missense_variant	1/15	1		ENSP00000342232.5	Q13263-2
TRIM28	ENST00000594806.5 linkuse as main transcript	c.-222-20G>T		intron_variant		5		ENSP00000473126.1	M0R3C0
TRIM28	ENST00000593582.5 linkuse as main transcript	c.77-507G>T		intron_variant		3		ENSP00000472586.1	M0R2I3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000299

AC:

AN:

33496

Hom.:

AF XY:

0.00

AC XY:

AN XY:

21172

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:

0.0000709

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000184

AC:

AN:

1253272

Hom.:

Cov.:

AF XY:

0.0000211

AC XY:

AN XY:

616484

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:

0.0000161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wilms tumor 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

Nov 03, 2022

The TRIM28 c.161G>T (p.Gly54Val) missense change has a maximum subpopulation frequency of 0.0071% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with a personal or family history of Wilms tumor. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.57

T;T

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.34

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.071

Sift

Uncertain

0.0030

D;T

Sift4G

Uncertain

0.010

D;D

Polyphen

0.093

B;B

Vest4

0.13

MutPred

0.19

Loss of relative solvent accessibility (P = 0.0306);Loss of relative solvent accessibility (P = 0.0306);

MVP

0.41

MPC

0.79

ClinPred

0.53

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.22

gMVP

0.30

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