11-6456548-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033278.4(TRIM3):​c.1178G>T​(p.Arg393Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,452 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRIM3
NM_033278.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.592
Variant links:
Genes affected
TRIM3 (HGNC:10064): (tripartite motif containing 3) The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also called the 'RING-B-box-coiled-coil' (RBCC) subgroup of RING finger proteins. 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. This protein localizes to cytoplasmic filaments. It is similar to a rat protein which is a specific partner for the tail domain of myosin V, a class of myosins which are involved in the targeted transport of organelles. The rat protein can also interact with alpha-actinin-4. Thus it is suggested that this human protein may play a role in myosin V-mediated cargo transport. Alternatively spliced transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM3NM_033278.4 linkc.1178G>T p.Arg393Leu missense_variant Exon 6 of 12 ENST00000345851.8 NP_150594.2 O75382-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM3ENST00000345851.8 linkc.1178G>T p.Arg393Leu missense_variant Exon 6 of 12 1 NM_033278.4 ENSP00000340797.3 O75382-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1453452
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
721382
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
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.:
32
Alfa
AF:
0.0000332
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1178G>T (p.R393L) alteration is located in exon 7 (coding exon 5) of the TRIM3 gene. This alteration results from a G to T substitution at nucleotide position 1178, causing the arginine (R) at amino acid position 393 to be replaced by a leucine (L). 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
0.11
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.61
D;D;.;D;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.55
D
LIST_S2
Uncertain
0.92
.;.;D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.52
D;D;D;D;D
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.1
L;L;.;L;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.3
D;D;D;D;.
REVEL
Uncertain
0.43
Sift
Benign
0.087
T;T;T;T;.
Sift4G
Benign
0.080
T;T;T;T;.
Polyphen
0.75
P;P;.;P;.
Vest4
0.66
MVP
0.36
MPC
2.1
ClinPred
0.98
D
GERP RS
4.2
Varity_R
0.30
gMVP
0.72

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: rs376023603; hg19: chr11-6477778; API