1-114407078-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015906.4(TRIM33):​c.2281G>A​(p.Ala761Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TRIM33
NM_015906.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24
Variant links:
Genes affected
TRIM33 (HGNC:16290): (tripartite motif containing 33) The protein encoded by this gene is thought to be a transcriptional corepressor. However, molecules that interact with this protein have not yet been identified. The protein is a member of the tripartite motif family. This motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.054066777).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM33NM_015906.4 linkc.2281G>A p.Ala761Thr missense_variant Exon 14 of 20 ENST00000358465.7 NP_056990.3 Q9UPN9-1B3KN30

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM33ENST00000358465.7 linkc.2281G>A p.Ala761Thr missense_variant Exon 14 of 20 1 NM_015906.4 ENSP00000351250.2 Q9UPN9-1
TRIM33ENST00000369543.6 linkc.2281G>A p.Ala761Thr missense_variant Exon 14 of 19 1 ENSP00000358556.2 Q9UPN9-2
TRIM33ENST00000448034.5 linkc.1561G>A p.Ala521Thr missense_variant Exon 12 of 18 5 ENSP00000402333.1 H0Y612
TRIM33ENST00000476908.1 linkn.-111G>A upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250818
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135580
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461222
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726922
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2281G>A (p.A761T) alteration is located in exon 14 (coding exon 14) of the TRIM33 gene. This alteration results from a G to A substitution at nucleotide position 2281, causing the alanine (A) at amino acid position 761 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
0.072
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.084
T;.
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.054
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.95
L;L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.20
N;N
REVEL
Benign
0.11
Sift
Benign
0.16
T;T
Sift4G
Benign
0.59
T;T
Polyphen
0.0
B;B
Vest4
0.042
MutPred
0.18
Gain of phosphorylation at A761 (P = 0.0103);Gain of phosphorylation at A761 (P = 0.0103);
MVP
0.23
MPC
0.53
ClinPred
0.21
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.024
gMVP
0.21

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: rs1335946045; hg19: chr1-114949700; API