Variant 11-89801738-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_020358.2(TRIM49):c.702C>G(p.Asn234Lys) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 11)

Exomes 𝑓: 0.00028 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49
NM_020358.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0140

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063311756).

BP6

Variant 11-89801738-G-C is Benign according to our data. Variant chr11-89801738-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2386953.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM49	NM_020358.2 linkuse as main transcript	c.702C>G	p.Asn234Lys	missense_variant	5/8	ENST00000329758.5	NP_065091.1
TRIM49	XM_024448617.2 linkuse as main transcript	c.702C>G	p.Asn234Lys	missense_variant	3/6		XP_024304385.1
TRIM49	XM_017018027.3 linkuse as main transcript	c.508-750C>G		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.702C>G	p.Asn234Lys	missense_variant	5/8	1	NM_020358.2	ENSP00000327604	A2
TRIM49	ENST00000532501.2 linkuse as main transcript	c.508-750C>G		intron_variant		5		ENSP00000431618	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

136

AN:

94682

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000306

Gnomad SAS

AF:

0.000390

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000910

Gnomad OTH

AF:

0.00175

GnomAD3 exomes

AF:

0.0000948

AC:

AN:

10548

Hom.:

AF XY:

0.00

AC XY:

AN XY:

5948

show subpopulations

Gnomad AFR exome

AF:

0.00336

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:

0.000282

AC:

157

AN:

557546

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

AN XY:

286476

show subpopulations

Gnomad4 AFR exome

AF:

0.00606

Gnomad4 AMR exome

AF:

0.0000532

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000243

Gnomad4 SAS exome

AF:

0.000362

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000818

Gnomad4 OTH exome

AF:

0.000478

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00142

AC:

135

AN:

94790

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

AN XY:

44700

show subpopulations

Gnomad4 AFR

AF:

0.00498

Gnomad4 AMR

AF:

0.000313

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000308

Gnomad4 SAS

AF:

0.000391

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000910

Gnomad4 OTH

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.12

DANN

Benign

0.16

DEOGEN2

Benign

0.00078

Eigen

Benign

-2.5

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.000080

LIST_S2

Benign

0.023

M_CAP

Benign

0.00048

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

2.0

REVEL

Benign

0.018

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.041

MutPred

0.41

Gain of ubiquitination at N234 (P = 0.0162);

MVP

0.043

MPC

2.1

ClinPred

0.011

GERP RS

-1.8

Varity_R

0.025

gMVP

0.026

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