chr1-155175986-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_025058.5(TRIM46):c.424C>T(p.Arg142Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,278 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 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
TRIM46
NM_025058.5 missense
NM_025058.5 missense
Scores
6
6
6
Clinical Significance
Conservation
PhyloP100: 0.690
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 Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TRIM46
BP4
?
Computational evidence support a benign effect (MetaRNN=0.06585285).
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM46 | NM_025058.5 | c.424C>T | p.Arg142Trp | missense_variant | 3/10 | ENST00000334634.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM46 | ENST00000334634.9 | c.424C>T | p.Arg142Trp | missense_variant | 3/10 | 1 | NM_025058.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152128Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000164 AC: 41AN: 250632Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135420
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GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461150Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 65AN XY: 726758
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GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74322
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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 | Dec 07, 2023 | The c.424C>T (p.R142W) alteration is located in exon 3 (coding exon 3) of the TRIM46 gene. This alteration results from a C to T substitution at nucleotide position 424, causing the arginine (R) at amino acid position 142 to be replaced by a tryptophan (W). 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
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;.;.;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;.;D;.;D;D;D;.
REVEL
Uncertain
Sift
Pathogenic
D;.;D;.;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;D;.;D;.
Vest4
MVP
MPC
1.8
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