1-155175558-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025058.5(TRIM46):​c.236C>G​(p.Ser79Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,708 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: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRIM46
NM_025058.5 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3190763).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM46NM_025058.5 linkc.236C>G p.Ser79Cys 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.236C>G p.Ser79Cys missense_variant Exon 2 of 10 1 NM_025058.5 ENSP00000334657.4 Q7Z4K8-1
ENSG00000273088ENST00000473363.3 linkc.49-2084G>C intron_variant Intron 1 of 4 5 ENSP00000477381.3 V9GZ38

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1454708
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
723578
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.236C>G (p.S79C) alteration is located in exon 2 (coding exon 2) of the TRIM46 gene. This alteration results from a C to G substitution at nucleotide position 236, causing the serine (S) at amino acid position 79 to be replaced by a cysteine (C). 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
Uncertain
0.49
BayesDel_addAF
Benign
-0.0021
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.027
.;.;.;T;.;T;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.32
T;T;T;T;T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.4
.;M;M;.;.;M;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-2.5
.;D;.;N;N;N;.
REVEL
Benign
0.12
Sift
Benign
0.13
.;T;.;T;D;D;.
Sift4G
Uncertain
0.0030
D;D;D;D;D;D;D
Polyphen
1.0, 0.014
.;D;.;B;.;B;.
Vest4
0.49
MutPred
0.23
.;Loss of glycosylation at S79 (P = 0.0044);Loss of glycosylation at S79 (P = 0.0044);Loss of glycosylation at S79 (P = 0.0044);.;Loss of glycosylation at S79 (P = 0.0044);.;
MVP
0.48
MPC
1.8
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.25
gMVP
0.49

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: chr1-155148034; COSMIC: COSV55278720; COSMIC: COSV55278720; API