1-114424726-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015906.4(TRIM33):​c.1725G>T​(p.Met575Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 6.9e-7 ( 0 hom. )

Consequence

TRIM33
NM_015906.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19
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 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=0.15406778).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM33NM_015906.4 linkc.1725G>T p.Met575Ile missense_variant Exon 10 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.1725G>T p.Met575Ile missense_variant Exon 10 of 20 1 NM_015906.4 ENSP00000351250.2 Q9UPN9-1
TRIM33ENST00000369543.6 linkc.1725G>T p.Met575Ile missense_variant Exon 10 of 19 1 ENSP00000358556.2 Q9UPN9-2
TRIM33ENST00000448034.5 linkc.933G>T p.Met311Ile missense_variant Exon 7 of 18 5 ENSP00000402333.1 H0Y612

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1452240
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
722366
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:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1725G>T (p.M575I) alteration is located in exon 10 (coding exon 10) of the TRIM33 gene. This alteration results from a G to T substitution at nucleotide position 1725, causing the methionine (M) at amino acid position 575 to be replaced by an isoleucine (I). 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
Uncertain
0.38
BayesDel_addAF
Uncertain
0.022
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.14
T;.
Eigen
Benign
0.19
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.84
N;N
REVEL
Benign
0.16
Sift
Benign
0.35
T;T
Sift4G
Benign
0.41
T;T
Polyphen
0.14
B;B
Vest4
0.27
MutPred
0.35
Loss of MoRF binding (P = 0.0921);Loss of MoRF binding (P = 0.0921);
MVP
0.46
MPC
0.58
ClinPred
0.45
T
GERP RS
5.6
Varity_R
0.15
gMVP
0.066

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: rs771084521; hg19: chr1-114967348; API