rs1349828305

Variant summary

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

The NM_033278.4(TRIM3):​c.830G>C​(p.Arg277Pro) 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 1,460,080 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R277Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

TRIM3
NM_033278.4 missense

Scores

3
13
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56
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 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.830G>C p.Arg277Pro 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.830G>C p.Arg277Pro missense_variant Exon 6 of 12 1 NM_033278.4 ENSP00000340797.3 O75382-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460080
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
726508
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.69
D;D;.;D;.
Eigen
Benign
0.052
Eigen_PC
Benign
0.17
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
.;.;D;D;D
M_CAP
Uncertain
0.086
D
MetaRNN
Uncertain
0.63
D;D;D;D;D
MetaSVM
Uncertain
-0.053
T
MutationAssessor
Uncertain
2.0
M;M;.;M;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-4.1
D;D;D;D;.
REVEL
Uncertain
0.53
Sift
Uncertain
0.0020
D;D;D;D;.
Sift4G
Uncertain
0.0040
D;D;D;D;.
Polyphen
0.0070
B;B;.;B;.
Vest4
0.81
MutPred
0.53
Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);.;Loss of MoRF binding (P = 0.0052);.;
MVP
0.82
MPC
1.5
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.88
gMVP
0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-6478126; API