chr1-155175590-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_025058.5(TRIM46):​c.268C>A​(p.Arg90Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,690 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TRIM46
NM_025058.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.36845657).
BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM46NM_025058.5 linkc.268C>A p.Arg90Ser missense_variant Exon 2 of 10 ENST00000334634.9 NP_079334.3 Q7Z4K8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM46ENST00000334634.9 linkc.268C>A p.Arg90Ser missense_variant Exon 2 of 10 1 NM_025058.5 ENSP00000334657.4 Q7Z4K8-1
ENSG00000273088ENST00000473363.3 linkc.49-2116G>T intron_variant Intron 1 of 4 5 ENSP00000477381.3 V9GZ38

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
247916
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134692
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000359
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461496
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
727062
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:
0.0000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.268C>A (p.R90S) alteration is located in exon 2 (coding exon 2) of the TRIM46 gene. This alteration results from a C to A substitution at nucleotide position 268, causing the arginine (R) at amino acid position 90 to be replaced by a serine (S). 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
Pathogenic
0.95
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.020
.;.;.;T;.;T;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.37
T;T;T;T;T;T;T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
1.9
.;L;L;.;.;L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.2
.;N;.;N;N;N;.
REVEL
Benign
0.25
Sift
Benign
0.058
.;T;.;T;T;T;.
Sift4G
Benign
0.088
T;T;T;T;T;T;T
Polyphen
1.0
.;D;.;D;.;D;.
Vest4
0.51
MutPred
0.43
.;Gain of phosphorylation at R90 (P = 9e-04);Gain of phosphorylation at R90 (P = 9e-04);Gain of phosphorylation at R90 (P = 9e-04);.;Gain of phosphorylation at R90 (P = 9e-04);.;
MVP
0.27
MPC
1.9
ClinPred
0.75
D
GERP RS
4.5
Varity_R
0.54
gMVP
0.42

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: rs779977977; hg19: chr1-155148066; API