7-138460889-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015905.3(TRIM24):​c.341G>T​(p.Gly114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000081 in 1,517,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

TRIM24
NM_015905.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.857
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09304047).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRIM24NM_015905.3 linkuse as main transcriptc.341G>T p.Gly114Val missense_variant 1/19 ENST00000343526.9 NP_056989.2 O15164-1
TRIM24NM_003852.4 linkuse as main transcriptc.341G>T p.Gly114Val missense_variant 1/19 NP_003843.3 O15164-2A0A024R784

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIM24ENST00000343526.9 linkuse as main transcriptc.341G>T p.Gly114Val missense_variant 1/191 NM_015905.3 ENSP00000340507.4 O15164-1
TRIM24ENST00000415680.6 linkuse as main transcriptc.341G>T p.Gly114Val missense_variant 1/191 ENSP00000390829.2 O15164-2

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152040
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000236
AC:
3
AN:
127384
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
72770
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000546
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000857
AC:
117
AN:
1365530
Hom.:
0
Cov.:
32
AF XY:
0.0000991
AC XY:
67
AN XY:
676278
show subpopulations
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:
0.0000941
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152148
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000319
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2021The c.341G>T (p.G114V) alteration is located in exon 1 (coding exon 1) of the TRIM24 gene. This alteration results from a G to T substitution at nucleotide position 341, causing the glycine (G) at amino acid position 114 to be replaced by a valine (V). 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
0.087
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.16
T;.
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.74
T;T
M_CAP
Pathogenic
0.37
D
MetaRNN
Benign
0.093
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.12
Sift
Uncertain
0.0070
D;D
Sift4G
Benign
0.13
T;T
Polyphen
0.0010
B;B
Vest4
0.20
MVP
0.37
MPC
0.76
ClinPred
0.18
T
GERP RS
1.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.39

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs551903708; hg19: chr7-138145634; API