Variant 11-120125743-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012101.4(TRIM29):c.1281G>A(p.Met427Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

TRIM29
NM_012101.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

Variant links:

Genes affected

TRIM29 (HGNC:17274): (tripartite motif containing 29) The protein encoded by this gene belongs to the TRIM protein family. It has multiple zinc finger motifs and a leucine zipper motif. It has been proposed to form homo- or heterodimers which are involved in nucleic acid binding. Thus, it may act as a transcriptional regulatory factor involved in carcinogenesis and/or differentiation. It may also function in the suppression of radiosensitivity since it is associated with ataxia telangiectasia phenotype. [provided by RefSeq, Jul 2008]

TRIM29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1296305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM29	NM_012101.4 linkuse as main transcript	c.1281G>A	p.Met427Ile	missense_variant	4/9	ENST00000341846.10	NP_036233.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM29	ENST00000341846.10 linkuse as main transcript	c.1281G>A	p.Met427Ile	missense_variant	4/9	1	NM_012101.4	ENSP00000343129	P1	Q14134-1
TRIM29	ENST00000529044.5 linkuse as main transcript	c.498G>A	p.Met166Ile	missense_variant	4/9	2		ENSP00000436015
TRIM29	ENST00000530470.1 linkuse as main transcript	n.615G>A		non_coding_transcript_exon_variant	1/2	2
TRIM29	ENST00000475051.4 linkuse as main transcript	c.*619G>A		3_prime_UTR_variant, NMD_transcript_variant	5/10	5		ENSP00000433779

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251186

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.0000617

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000732

AC:

107

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000926

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.1281G>A (p.M427I) alteration is located in exon 4 (coding exon 4) of the TRIM29 gene. This alteration results from a G to A substitution at nucleotide position 1281, causing the methionine (M) at amino acid position 427 to be replaced by an isoleucine (I). 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

0.57

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0073

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.0020

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;.

MutationTaster

Benign

0.68

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.060

Sift

Benign

0.83

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.37

MutPred

0.76

Gain of catalytic residue at L432 (P = 0.0478);.;

MVP

0.20

MPC

0.23

ClinPred

0.069

GERP RS

4.5

Varity_R

0.14

gMVP

0.43

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.

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