Variant 11-89801737-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020358.2(TRIM49):c.703G>A(p.Glu235Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., cov: 11)

Exomes 𝑓: 0.00051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49
NM_020358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.66

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064789653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM49	NM_020358.2 linkuse as main transcript	c.703G>A	p.Glu235Lys	missense_variant	5/8	ENST00000329758.5	NP_065091.1
TRIM49	XM_024448617.2 linkuse as main transcript	c.703G>A	p.Glu235Lys	missense_variant	3/6		XP_024304385.1
TRIM49	XM_017018027.3 linkuse as main transcript	c.508-749G>A		intron_variant			XP_016873516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49	ENST00000329758.5 linkuse as main transcript	c.703G>A	p.Glu235Lys	missense_variant	5/8	1	NM_020358.2	ENSP00000327604	A2
TRIM49	ENST00000532501.2 linkuse as main transcript	c.508-749G>A		intron_variant		5		ENSP00000431618	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

339

AN:

95060

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00239

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000391

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00260

GnomAD3 exomes

AF:

0.000818

AC:

AN:

9778

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

5558

show subpopulations

Gnomad AFR exome

AF:

0.00847

Gnomad AMR exome

AF:

0.000670

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000782

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00625

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000506

AC:

278

AN:

548982

Hom.:

Cov.:

AF XY:

0.000478

AC XY:

135

AN XY:

282270

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000352

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000305

Gnomad4 OTH exome

AF:

0.000973

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00359

AC:

342

AN:

95168

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

167

AN XY:

44876

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.00239

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000392

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00256

Alfa

AF:

0.00236

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

Aug 02, 2021

The c.703G>A (p.E235K) alteration is located in exon 5 (coding exon 3) of the TRIM49 gene. This alteration results from a G to A substitution at nucleotide position 703, causing the glutamic acid (E) at amino acid position 235 to be replaced by a lysine (K). 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

0.079

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.95

DANN

Benign

0.83

DEOGEN2

Benign

0.038

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.19

M_CAP

Benign

0.00093

MetaRNN

Benign

0.0065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

REVEL

Benign

0.0050

Sift

Benign

0.18

Sift4G

Benign

0.17

Polyphen

0.033

Vest4

0.060

MVP

0.043

MPC

2.1

ClinPred

0.0025

GERP RS

-0.11

Varity_R

0.040

gMVP

0.060

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