Variant chr1-155175903-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_025058.5(TRIM46):c.341C>T(p.Pro114Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000189 in 1,589,424 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: 0.0000014 ( 0 hom. )

Consequence

TRIM46
NM_025058.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.97

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, TRIM46

BP4

Computational evidence support a benign effect (MetaRNN=0.3720613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM46	NM_025058.5 linkuse as main transcript	c.341C>T	p.Pro114Leu	missense_variant	3/10	ENST00000334634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM46	ENST00000334634.9 linkuse as main transcript	c.341C>T	p.Pro114Leu	missense_variant	3/10	1	NM_025058.5	P1	Q7Z4K8-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000431

AC:

AN:

232260

Hom.:

AF XY:

0.00000802

AC XY:

AN XY:

124682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1437172

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

711834

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000824

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Feb 14, 2023

The c.341C>T (p.P114L) 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 341, causing the proline (P) at amino acid position 114 to be replaced by a leucine (L). 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

0.65

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

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

M_CAP

Benign

0.040

MetaRNN

Benign

0.37

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

MetaSVM

Benign

-0.68

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.75

REVEL

Benign

0.21

Sift4G

Uncertain

0.014

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

Polyphen

1.0, 0.94, 0.42

.;D;.;P;.;B;.

Vest4

0.57

MutPred

0.56

.;Gain of catalytic residue at P114 (P = 0.0135);Gain of catalytic residue at P114 (P = 0.0135);Gain of catalytic residue at P114 (P = 0.0135);.;Gain of catalytic residue at P114 (P = 0.0135);.;

MVP

0.53

MPC

1.8

ClinPred

0.99

GERP RS

4.5

Varity_R

0.43

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over