Variant 11-89799742-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_020358.2(TRIM49):c.833T>C(p.Leu278Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 1 hom., cov: 21)

Exomes 𝑓: 0.00022 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49
NM_020358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30193645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM49	NM_020358.2 linkuse as main transcript	c.833T>C	p.Leu278Pro	missense_variant	7/8	ENST00000329758.5	NP_065091.1
TRIM49	XM_017018027.3 linkuse as main transcript	c.602T>C	p.Leu201Pro	missense_variant	4/5		XP_016873516.1
TRIM49	XM_024448617.2 linkuse as main transcript	c.738+1960T>C		intron_variant			XP_024304385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49	ENST00000329758.5 linkuse as main transcript	c.833T>C	p.Leu278Pro	missense_variant	7/8	1	NM_020358.2	ENSP00000327604	A2
TRIM49	ENST00000532501.2 linkuse as main transcript	c.602T>C	p.Leu201Pro	missense_variant	5/6	5		ENSP00000431618	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

137098

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000901

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000106

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000469

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000150

AC:

AN:

86786

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

45986

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000273

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000306

Gnomad OTH exome

AF:

0.000380

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000218

AC:

285

AN:

1304990

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

154

AN XY:

644266

show subpopulations

Gnomad4 AFR exome

AF:

0.0000717

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000505

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000180

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.000221

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000248

AC:

AN:

137098

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

AN XY:

66380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000901

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000106

Gnomad4 NFE

AF:

0.000469

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.000204

ExAC

AF:

0.0000546

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

Jul 20, 2022

The c.833T>C (p.L278P) alteration is located in exon 7 (coding exon 5) of the TRIM49 gene. This alteration results from a T to C substitution at nucleotide position 833, causing the leucine (L) at amino acid position 278 to be replaced by a proline (P). 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

0.72

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.023

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.00093

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Benign

0.060

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

0.20

B;.

Vest4

0.31

MutPred

0.79

Gain of disorder (P = 0.0099);.;

MVP

0.043

MPC

2.8

ClinPred

0.33

GERP RS

0.82

Varity_R

0.61

gMVP

0.24

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