Variant chr11-89798233-G-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_020358.2(TRIM49):c.1256C>A(p.Thr419Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,566,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

TRIM49
NM_020358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.86

Variant links:

Genes affected

TRIM49 (HGNC:13431): (tripartite motif containing 49) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This gene has been found to be preferentially expressed in testis. Related pseudogenes and gene duplicates have also been identified on chromosome 11. [provided by RefSeq, Aug 2010]

TRIM49 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=0.23545492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRIM49	NM_020358.2 linkuse as main transcript	c.1256C>A	p.Thr419Asn	missense_variant	8/8	ENST00000329758.5
TRIM49	XM_017018027.3 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	5/5
TRIM49	XM_024448617.2 linkuse as main transcript	c.738+3469C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM49	ENST00000329758.5 linkuse as main transcript	c.1256C>A	p.Thr419Asn	missense_variant	8/8	1	NM_020358.2	A2
TRIM49	ENST00000532501.2 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	6/6	5		P2

Frequencies

GnomAD3 genomes

AF:

0.0000326

AC:

AN:

122552

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:

0.000261

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000497

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000343

AC:

AN:

233148

Hom.:

AF XY:

0.0000315

AC XY:

AN XY:

127072

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:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000468

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000256

AC:

AN:

1443990

Hom.:

Cov.:

AF XY:

0.0000362

AC XY:

AN XY:

718242

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:

0.000269

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000326

AC:

AN:

122634

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

58734

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:

0.000260

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000497

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000674

AC:

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

Sep 20, 2023

The c.1256C>A (p.T419N) alteration is located in exon 8 (coding exon 6) of the TRIM49 gene. This alteration results from a C to A substitution at nucleotide position 1256, causing the threonine (T) at amino acid position 419 to be replaced by an asparagine (N). 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

Benign

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.093

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.17

T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.42

B;.

Vest4

0.14

MutPred

0.47

Gain of catalytic residue at T419 (P = 0.1073);.;

MVP

0.11

MPC

1.7

ClinPred

0.61

GERP RS

-1.7

Varity_R

0.32

gMVP

0.076

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