chr1-114427278-C-T

Variant summary

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

The NM_015906.4(TRIM33):​c.1319G>A​(p.Arg440His) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,574,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

TRIM33
NM_015906.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.20927459).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM33NM_015906.4 linkc.1319G>A p.Arg440His missense_variant Exon 8 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.1319G>A p.Arg440His missense_variant Exon 8 of 20 1 NM_015906.4 ENSP00000351250.2 Q9UPN9-1
TRIM33ENST00000369543.6 linkc.1319G>A p.Arg440His missense_variant Exon 8 of 19 1 ENSP00000358556.2 Q9UPN9-2
TRIM33ENST00000448034.5 linkc.527G>A p.Arg176His missense_variant Exon 5 of 18 5 ENSP00000402333.1 H0Y612

Frequencies

GnomAD3 genomes
AF:
0.00000662
AC:
1
AN:
151142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000126
AC:
3
AN:
238290
Hom.:
0
AF XY:
0.0000155
AC XY:
2
AN XY:
128710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000321
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000565
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000911
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000913
AC:
13
AN:
1423568
Hom.:
0
Cov.:
25
AF XY:
0.00000990
AC XY:
7
AN XY:
706812
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000239
Gnomad4 ASJ exome
AF:
0.0000396
Gnomad4 EAS exome
AF:
0.0000513
Gnomad4 SAS exome
AF:
0.0000248
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000644
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000662
AC:
1
AN:
151142
Hom.:
0
Cov.:
32
AF XY:
0.0000136
AC XY:
1
AN XY:
73680
show subpopulations
Gnomad4 AFR
AF:
0.0000243
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
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
Nov 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1319G>A (p.R440H) alteration is located in exon 8 (coding exon 8) of the TRIM33 gene. This alteration results from a G to A substitution at nucleotide position 1319, causing the arginine (R) at amino acid position 440 to be replaced by a histidine (H). 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
0.56
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.36
N;N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.32
Sift
Benign
0.18
T;T
Sift4G
Benign
0.29
T;T
Polyphen
0.062
B;B
Vest4
0.33
MutPred
0.46
Loss of MoRF binding (P = 0.0096);Loss of MoRF binding (P = 0.0096);
MVP
0.41
MPC
1.5
ClinPred
0.68
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.85

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: rs755058963; hg19: chr1-114969900; COSMIC: COSV61822813; API