7-138460624-G-A

Position:

• chr7-138460624-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000343526.9(TRIM24):​c.76G>A​(p.Ala26Thr) 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 Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM24 ENST00000343526.9 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16499066).
• BP6: Variant 7-138460624-G-A is Benign according to our data. Variant chr7-138460624-G-A is described in ClinVar as [Benign]. Clinvar id is 2445236.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM24	NM_015905.3	c.76G>A	p.Ala26Thr	missense_variant	1/19	ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4	c.76G>A	p.Ala26Thr	missense_variant	1/19		NP_003843.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9	c.76G>A	p.Ala26Thr	missense_variant	1/19	1	NM_015905.3	ENSP00000340507	P4
TRIM24	ENST00000415680.6	c.76G>A	p.Ala26Thr	missense_variant	1/19	1		ENSP00000390829	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1261416 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 618434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ovarian cancer Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.61	T;T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.077
Sift	Benign	0.054	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.16	B;B
Vest4		0.14
MutPred		0.15		Gain of glycosylation at A26 (P = 8e-04);Gain of glycosylation at A26 (P = 8e-04);
MVP		0.36
MPC		1.5
ClinPred		0.19	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2
Varity_R		0.048
gMVP		0.41

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: chr7-138145369;