Variant chr11-89799718-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000329758.5(TRIM49):c.857G>A(p.Arg286Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R286G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49
ENST00000329758.5 missense, splice_region

Scores

Splicing: ADA: 0.00001267

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.93

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14723048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49	NM_020358.2 linkuse as main transcript	c.857G>A	p.Arg286Gln	missense_variant, splice_region_variant	7/8	ENST00000329758.5	NP_065091.1	P0CI25
TRIM49	XM_017018027.3 linkuse as main transcript	c.626G>A	p.Arg209Gln	missense_variant, splice_region_variant	4/5		XP_016873516.1	E9PK69
TRIM49	XM_024448617.2 linkuse as main transcript	c.738+1984G>A		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.857G>A	p.Arg286Gln	missense_variant, splice_region_variant	7/8	1	NM_020358.2	ENSP00000327604.1		P0CI25
TRIM49	ENST00000532501.2 linkuse as main transcript	c.626G>A	p.Arg209Gln	missense_variant, splice_region_variant	5/6	5		ENSP00000431618.2		E9PK69

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

134504

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000299

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

72390

Hom.:

AF XY:

0.00

AC XY:

AN XY:

37992

show subpopulations

Gnomad AFR exome

AF:

0.000385

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000799

AC:

AN:

1126488

Hom.:

Cov.:

AF XY:

0.00000893

AC XY:

AN XY:

560134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000848

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:

0.00000703

Gnomad4 OTH exome

AF:

0.0000208

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000743

AC:

AN:

134504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64950

show subpopulations

Gnomad4 AFR

AF:

0.0000299

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

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 19, 2023

The c.857G>A (p.R286Q) alteration is located in exon 7 (coding exon 5) of the TRIM49 gene. This alteration results from a G to A substitution at nucleotide position 857, causing the arginine (R) at amino acid position 286 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.73

DANN

Benign

0.33

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.00092

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.86

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.065

Sift

Benign

0.21

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0090

B;.

Vest4

0.050

MutPred

0.82

Loss of catalytic residue at R286 (P = 0.1606);.;

MVP

0.043

MPC

2.1

ClinPred

0.014

GERP RS

-1.5

Varity_R

0.034

gMVP

0.023

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000013

dbscSNV1_RF

Benign

0.036

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