7-138504404-A-C

Position:

• chr7-138504404-A-C

Variant summary

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

The ENST00000343526.9(TRIM24):​c.479A>C​(p.Asn160Thr) 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. 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: 31)
• Consequence: TRIM24 ENST00000343526.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

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=0.12828216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM24	NM_015905.3	c.479A>C	p.Asn160Thr	missense_variant	2/19	ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4	c.479A>C	p.Asn160Thr	missense_variant	2/19		NP_003843.3
TRIM24	XM_024446981.2	c.422A>C	p.Asn141Thr	missense_variant	2/19		XP_024302749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9	c.479A>C	p.Asn160Thr	missense_variant	2/19	1	NM_015905.3	ENSP00000340507	P4
TRIM24	ENST00000415680.6	c.479A>C	p.Asn160Thr	missense_variant	2/19	1		ENSP00000390829	A2
TRIM24	ENST00000497516.5	n.353A>C		non_coding_transcript_exon_variant	2/11	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

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

Jan 26, 2022

The c.479A>C (p.N160T) alteration is located in exon 2 (coding exon 2) of the TRIM24 gene. This alteration results from a A to C substitution at nucleotide position 479, causing the asparagine (N) at amino acid position 160 to be replaced by a threonine (T). 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	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.075	N;N
MutationTaster	Benign	0.83	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.032
Sift	Benign	0.63	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0060	B;B
Vest4		0.16
MutPred		0.45		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.23
MPC		0.65
ClinPred		0.61	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
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: chr7-138189149;