7-138460844-C-G

Position:

• chr7-138460844-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000343526.9(TRIM24):​c.296C>G​(p.Ala99Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM24 ENST00000343526.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.302

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20734692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM24	NM_015905.3	c.296C>G	p.Ala99Gly	missense_variant	1/19	ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4	c.296C>G	p.Ala99Gly	missense_variant	1/19		NP_003843.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9	c.296C>G	p.Ala99Gly	missense_variant	1/19	1	NM_015905.3	ENSP00000340507	P4
TRIM24	ENST00000415680.6	c.296C>G	p.Ala99Gly	missense_variant	1/19	1		ENSP00000390829	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.296C>G (p.A99G) alteration is located in exon 1 (coding exon 1) of the TRIM24 gene. This alteration results from a C to G substitution at nucleotide position 296, causing the alanine (A) at amino acid position 99 to be replaced by a glycine (G). 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	0.072
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.084	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.64	T;T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	0.90	N;N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.33	N;N
REVEL	Benign	0.18
Sift	Benign	0.074	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0020	B;D
Vest4		0.10
MutPred		0.18		Loss of glycosylation at P102 (P = 0.1847);Loss of glycosylation at P102 (P = 0.1847);
MVP		0.57
MPC		0.72
ClinPred		0.12	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-138145589;