Variant 7-138551078-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The ENST00000343526.9(TRIM24):c.1159C>T(p.Arg387Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TRIM24
ENST00000343526.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

TRIM24 (HGNC:11812): (tripartite motif containing 24) The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains - a RING, a B-box type 1 and a B-box type 2 - and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

TRIM24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM24	NM_015905.3 linkuse as main transcript	c.1159C>T	p.Arg387Trp	missense_variant	8/19	ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4 linkuse as main transcript	c.1159C>T	p.Arg387Trp	missense_variant	8/19		NP_003843.3
TRIM24	XM_024446981.2 linkuse as main transcript	c.1102C>T	p.Arg368Trp	missense_variant	8/19		XP_024302749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9 linkuse as main transcript	c.1159C>T	p.Arg387Trp	missense_variant	8/19	1	NM_015905.3	ENSP00000340507	P4	O15164-1
TRIM24	ENST00000415680.6 linkuse as main transcript	c.1159C>T	p.Arg387Trp	missense_variant	8/19	1		ENSP00000390829	A2	O15164-2
TRIM24	ENST00000497516.5 linkuse as main transcript	n.1033C>T		non_coding_transcript_exon_variant	8/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251136

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135716

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461244

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726934

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.1159C>T (p.R387W) alteration is located in exon 8 (coding exon 8) of the TRIM24 gene. This alteration results from a C to T substitution at nucleotide position 1159, causing the arginine (R) at amino acid position 387 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

D;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Uncertain

-0.054

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.3

D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

1.0

D;D

Vest4

0.68

MutPred

0.51

Loss of MoRF binding (P = 0.0695);Loss of MoRF binding (P = 0.0695);

MVP

0.58

MPC

1.4

ClinPred

1.0

GERP RS

3.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.38

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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