Variant 7-138460592-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000343526.9(TRIM24):c.44C>T(p.Ala15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,325,538 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: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

TRIM24
ENST00000343526.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.268

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026925147).

BS2

High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM24	NM_015905.3 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	1/19	ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	1/19		NP_003843.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	1/19	1	NM_015905.3	ENSP00000340507	P4	O15164-1
TRIM24	ENST00000415680.6 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	1/19	1		ENSP00000390829	A2	O15164-2

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00104

AC:

AN:

2872

Hom.:

AF XY:

0.00108

AC XY:

AN XY:

1850

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:

0.00231

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000900

AC:

1056

AN:

1173534

Hom.:

Cov.:

AF XY:

0.000876

AC XY:

497

AN XY:

567228

show subpopulations

Gnomad4 AFR exome

AF:

0.000170

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:

0.000144

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.000333

GnomAD4 genome

AF:

0.000316

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000693

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000240

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

Aug 10, 2021

The c.44C>T (p.A15V) alteration is located in exon 1 (coding exon 1) of the TRIM24 gene. This alteration results from a C to T substitution at nucleotide position 44, causing the alanine (A) at amino acid position 15 to be replaced by a valine (V). 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

Benign

0.22

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.64

T;T

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.95

N;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.11

Sift

Benign

0.15

T;T

Sift4G

Uncertain

0.045

D;D

Polyphen

0.046

B;B

Vest4

0.11

MVP

0.46

MPC

1.6

ClinPred

0.071

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.61

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