11-6457014-G-C

Variant summary

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

The NM_033278.4(TRIM3):​c.712C>G​(p.Leu238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

TRIM3
NM_033278.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99
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]

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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=0.16765895).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM3NM_033278.4 linkc.712C>G p.Leu238Val 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.712C>G p.Leu238Val missense_variant Exon 6 of 12 1 NM_033278.4 ENSP00000340797.3 O75382-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.00048
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
9.5
DANN
Benign
0.85
DEOGEN2
Benign
0.15
T;T;.;T;.;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.45
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
.;.;D;D;D;D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
1.5
L;L;.;L;.;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.40
N;N;N;N;.;N
REVEL
Benign
0.10
Sift
Benign
0.28
T;T;T;T;.;T
Sift4G
Benign
0.46
T;T;T;T;.;.
Polyphen
0.058
B;B;.;B;.;.
Vest4
0.60
MutPred
0.35
Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);.;Loss of helix (P = 0.0376);.;Loss of helix (P = 0.0376);
MVP
0.41
MPC
2.2
ClinPred
0.25
T
GERP RS
-0.12
Varity_R
0.071
gMVP
0.35

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: rs955022236; hg19: chr11-6478244; API