7-138551121-A-G

Position:

• chr7-138551121-A-G

Variant summary

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

The ENST00000343526.9(TRIM24):​c.1202A>G​(p.Asn401Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM24 ENST00000343526.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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=0.2115444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM24	NM_015905.3	c.1202A>G	p.Asn401Ser	missense_variant	8/19	ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4	c.1202A>G	p.Asn401Ser	missense_variant	8/19		NP_003843.3
TRIM24	XM_024446981.2	c.1145A>G	p.Asn382Ser	missense_variant	8/19		XP_024302749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9	c.1202A>G	p.Asn401Ser	missense_variant	8/19	1	NM_015905.3	ENSP00000340507	P4
TRIM24	ENST00000415680.6	c.1202A>G	p.Asn401Ser	missense_variant	8/19	1		ENSP00000390829	A2
TRIM24	ENST00000497516.5	n.1076A>G		non_coding_transcript_exon_variant	8/11	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

Oct 10, 2023

The c.1202A>G (p.N401S) alteration is located in exon 8 (coding exon 8) of the TRIM24 gene. This alteration results from a A to G substitution at nucleotide position 1202, causing the asparagine (N) at amino acid position 401 to be replaced by a serine (S). 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	0.077
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.29
Sift	Benign	0.10	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.024	B;D
Vest4		0.30
MutPred		0.40		Gain of glycosylation at N401 (P = 0.0349);Gain of glycosylation at N401 (P = 0.0349);
MVP		0.74
MPC		0.54
ClinPred		0.73	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.83

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

Other links and lift over

dbSNP: rs935814087; hg19: chr7-138235866;