Genetic Variant TRIM49:p.Arg362Gln (chr11-89798404-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020358.2(TRIM49):c.1085G>A(p.Arg362Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,603,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

TRIM49
NM_020358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.218

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014789134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM49	NM_020358.2 link	c.1085G>A	p.Arg362Gln	missense_variant	Exon 8 of 8	ENST00000329758.5	NP_065091.1	P0CI25
TRIM49	XM_017018027.3 link	c.854G>A	p.Arg285Gln	missense_variant	Exon 5 of 5		XP_016873516.1	E9PK69
TRIM49	XM_024448617.2 link	c.738+3298G>A		intron_variant	Intron 3 of 5		XP_024304385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM49	ENST00000329758.5 link	c.1085G>A	p.Arg362Gln	missense_variant	Exon 8 of 8	1	NM_020358.2	ENSP00000327604.1		P0CI25
TRIM49	ENST00000532501.2 link	c.854G>A	p.Arg285Gln	missense_variant	Exon 6 of 6	5		ENSP00000431618.2		E9PK69

Frequencies

GnomAD3 genomes

AF:

0.000160

AC:

AN:

143610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.000214

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

250900

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.000684

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1459368

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

726040

show subpopulations

Gnomad4 AFR exome

AF:

0.000242

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000563

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.000174

AC:

AN:

143714

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

AN XY:

69976

show subpopulations

Gnomad4 AFR

AF:

0.000596

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000293

Gnomad4 EAS

AF:

0.000215

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1085G>A (p.R362Q) alteration is located in exon 8 (coding exon 6) of the TRIM49 gene. This alteration results from a G to A substitution at nucleotide position 1085, causing the arginine (R) at amino acid position 362 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

0.082

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0040

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.88

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.32

N;N

REVEL

Benign

0.013

Sift

Benign

0.54

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.012

B;.

Vest4

0.13

MVP

0.043

MPC

1.5

ClinPred

0.0091

GERP RS

-0.11

Varity_R

0.043

gMVP

0.036

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