Variant 19-58544871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005762.3(TRIM28):c.114C>T(p.Ala38Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,312,182 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 13 hom. )

Consequence

TRIM28
NM_005762.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.48

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 19-58544871-C-T is Benign according to our data. Variant chr19-58544871-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.48 with no splicing effect.

BS2

High AC in GnomAd4 at 326 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM28	NM_005762.3 linkuse as main transcript	c.114C>T	p.Ala38Ala	synonymous_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.114C>T	p.Ala38Ala	synonymous_variant	1/17	1	NM_005762.3	ENSP00000253024.4	Q13263-1
TRIM28	ENST00000341753.10 linkuse as main transcript	c.114C>T	p.Ala38Ala	synonymous_variant	1/15	1		ENSP00000342232.5	Q13263-2
TRIM28	ENST00000594806.5 linkuse as main transcript	c.-222-67C>T		intron_variant		5		ENSP00000473126.1	M0R3C0
TRIM28	ENST00000593582.5 linkuse as main transcript	c.77-554C>T		intron_variant		3		ENSP00000472586.1	M0R2I3

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

324

AN:

151584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.00327

AC:

AN:

8856

Hom.:

AF XY:

0.00387

AC XY:

AN XY:

5938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000876

Gnomad FIN exome

AF:

0.00174

Gnomad NFE exome

AF:

0.00565

Gnomad OTH exome

AF:

0.00746

GnomAD4 exome

AF:

0.00348

AC:

4034

AN:

1160490

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

1938

AN XY:

562948

show subpopulations

Gnomad4 AFR exome

AF:

0.000734

Gnomad4 AMR exome

AF:

0.000923

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.000425

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00413

GnomAD4 genome

AF:

0.00215

AC:

326

AN:

151692

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.000700

Gnomad4 AMR

AF:

0.000525

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00189

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	TRIM28: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -

TRIM28-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 03, 2023

This variant is classified as likely 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

-0.58

CADD

Benign

8.1

DANN

Benign

0.86

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