Genetic Variant TRIM24:p.Met360Leu (chr7-138538738-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015905.3(TRIM24):c.1078A>T(p.Met360Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M360V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRIM24
NM_015905.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.20

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13415518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM24	NM_015905.3 link	c.1078A>T	p.Met360Leu	missense_variant	Exon 7 of 19	ENST00000343526.9	NP_056989.2	O15164-1
TRIM24	NM_003852.4 link	c.1078A>T	p.Met360Leu	missense_variant	Exon 7 of 19		NP_003843.3	O15164-2A0A024R784
TRIM24	XM_024446981.2 link	c.1021A>T	p.Met341Leu	missense_variant	Exon 7 of 19		XP_024302749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM24	ENST00000343526.9 link	c.1078A>T	p.Met360Leu	missense_variant	Exon 7 of 19	1	NM_015905.3	ENSP00000340507.4	O15164-1
TRIM24	ENST00000415680.6 link	c.1078A>T	p.Met360Leu	missense_variant	Exon 7 of 19	1		ENSP00000390829.2	O15164-2
TRIM24	ENST00000497516.5 link	n.952A>T		non_coding_transcript_exon_variant	Exon 7 of 11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109628

Other (OTH)

AF:

0.00

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.20

N;N

PhyloP100

3.2

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.17

Sift

Benign

0.32

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0010

B;B

Vest4

0.36

MutPred

0.41

Loss of MoRF binding (P = 0.0794);Loss of MoRF binding (P = 0.0794);

MVP

0.21

MPC

0.57

ClinPred

0.70

GERP RS

4.4

Varity_R

0.15

gMVP

0.80

Mutation Taster

=92/8

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over