chr1-155178500-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_025058.5(TRIM46):c.1172G>A(p.Arg391Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000137 in 1,613,802 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: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
TRIM46
NM_025058.5 missense
NM_025058.5 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 5.04
Genes affected
TRIM46 (HGNC:19019): (tripartite motif containing 46) This gene encodes a protein of the tripartite motif (TRIM) family. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. TRIM46 is reported to be involved in the proliferation of multiple types of cancer cells including lung and breast cancer. It has also been shown to control neuronal polarity and axon specification by forming uniform microtubule bundles in the axon. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TRIM46
BP4
?
Computational evidence support a benign effect (MetaRNN=0.083767116).
BS2
?
High AC in GnomAd at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM46 | NM_025058.5 | c.1172G>A | p.Arg391Gln | missense_variant | 7/10 | ENST00000334634.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM46 | ENST00000334634.9 | c.1172G>A | p.Arg391Gln | missense_variant | 7/10 | 1 | NM_025058.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152154Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000191 AC: 48AN: 251146Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135774
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GnomAD4 exome AF: 0.000137 AC: 200AN: 1461648Hom.: 0 Cov.: 32 AF XY: 0.000132 AC XY: 96AN XY: 727150
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GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74326
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.1172G>A (p.R391Q) alteration is located in exon 7 (coding exon 7) of the TRIM46 gene. This alteration results from a G to A substitution at nucleotide position 1172, causing the arginine (R) at amino acid position 391 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;.;N;N;N;.
REVEL
Benign
Sift
Benign
T;.;T;.;T;T;T;.
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
0.079, 0.17, 0.099
.;.;B;.;B;.;B;.
Vest4
MVP
MPC
0.85
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at