7-138519305-G-A

Position:

• chr7-138519305-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000343526.9(TRIM24):​c.748G>A​(p.Glu250Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM24 ENST00000343526.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32855743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM24	NM_015905.3	c.748G>A	p.Glu250Lys	missense_variant	4/19	ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4	c.748G>A	p.Glu250Lys	missense_variant	4/19		NP_003843.3
TRIM24	XM_024446981.2	c.691G>A	p.Glu231Lys	missense_variant	4/19		XP_024302749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9	c.748G>A	p.Glu250Lys	missense_variant	4/19	1	NM_015905.3	ENSP00000340507	P4
TRIM24	ENST00000415680.6	c.748G>A	p.Glu250Lys	missense_variant	4/19	1		ENSP00000390829	A2
TRIM24	ENST00000464210.1	n.455G>A		non_coding_transcript_exon_variant	3/4	4
TRIM24	ENST00000497516.5	n.622G>A		non_coding_transcript_exon_variant	4/11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Feb 09, 2023

The c.748G>A (p.E250K) alteration is located in exon 4 (coding exon 4) of the TRIM24 gene. This alteration results from a G to A substitution at nucleotide position 748, causing the glutamic acid (E) at amino acid position 250 to be replaced by a lysine (K). 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	0.98
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.0089
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.21
Sift	Benign	0.15	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.12	B;D
Vest4		0.29
MutPred		0.56		Gain of methylation at E250 (P = 0.0395);Gain of methylation at E250 (P = 0.0395);
MVP		0.44
MPC		1.3
ClinPred		0.73	D
GERP RS		3.4
Varity_R		0.26
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr7-138204050;