dbSNP rs764575874: TRIM24:p.Met360Val (chr7-138538738-A-G) – 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>G(p.Met360Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)

Consequence

TRIM24
NM_015905.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

Publications

1 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=0.21641636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM24	NM_015905.3 link	c.1078A>G	p.Met360Val	missense_variant	Exon 7 of 19	ENST00000343526.9	NP_056989.2	O15164-1
TRIM24	NM_003852.4 link	c.1078A>G	p.Met360Val	missense_variant	Exon 7 of 19		NP_003843.3	O15164-2A0A024R784
TRIM24	XM_024446981.2 link	c.1021A>G	p.Met341Val	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>G	p.Met360Val	missense_variant	Exon 7 of 19	1	NM_015905.3	ENSP00000340507.4	O15164-1
TRIM24	ENST00000415680.6 link	c.1078A>G	p.Met360Val	missense_variant	Exon 7 of 19	1		ENSP00000390829.2	O15164-2
TRIM24	ENST00000497516.5 link	n.952A>G		non_coding_transcript_exon_variant	Exon 7 of 11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251388

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

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

Jul 09, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1078A>G (p.M360V) alteration is located in exon 7 (coding exon 7) of the TRIM24 gene. This alteration results from a A to G substitution at nucleotide position 1078, causing the methionine (M) at amino acid position 360 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

0.29

BayesDel_addAF

Benign

0.0051

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

N;N

PhyloP100

3.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.23

Sift

Benign

0.086

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.0010

B;B

Vest4

0.54

MutPred

0.45

Loss of catalytic residue at M360 (P = 0.045);Loss of catalytic residue at M360 (P = 0.045);

MVP

0.40

MPC

0.62

ClinPred

0.31

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.82

Mutation Taster

=94/6

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over