Genetic Variant TRIM46:p.Ser79Cys (chr1-155175558-C-G) – ACMG Classification: Uncertain_significance (1 pts)

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

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]

TRIM46 links:

ENSG00000273088 (HGNC:):

ENSG00000273088 links:

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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
TRIM46	NM_025058.5 link	c.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
TRIM46	ENST00000334634.9 link	c.236C>G	p.Ser79Cys	missense_variant	Exon 2 of 10	1	NM_025058.5	ENSP00000334657.4		Q7Z4K8-1
ENSG00000273088	ENST00000473363.3 link	c.49-2084G>C		intron_variant	Intron 1 of 4	5		ENSP00000477381.3		V9GZ38

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

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

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.32

T;T;T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.4

.;M;M;.;.;M;.

PrimateAI

Uncertain

0.64

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over