Variant 11-90039888-T-C 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_001195234.1(TRIM49C):c.785T>C(p.Met262Thr) 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 0.00013 ( 4 hom., cov: 17)

Exomes 𝑓: 0.00013 ( 23 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49C
NM_001195234.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.470

Variant links:

Genes affected

TRIM49C (HGNC:38877): (tripartite motif containing 49C) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM49C 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=0.007383138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM49C	NM_001195234.1 linkuse as main transcript	c.785T>C	p.Met262Thr	missense_variant	7/8	ENST00000448984.1	NP_001182163.1
TRIM49C	XM_017018126.2 linkuse as main transcript	c.554T>C	p.Met185Thr	missense_variant	4/5		XP_016873615.1
TRIM49C	XM_024448656.2 linkuse as main transcript	c.738+1909T>C		intron_variant			XP_024304424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49C	ENST00000448984.1 linkuse as main transcript	c.785T>C	p.Met262Thr	missense_variant	7/8	1	NM_001195234.1	ENSP00000388299	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111814

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00410

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:

0.000748

AC:

AN:

54846

Hom.:

AF XY:

0.000754

AC XY:

AN XY:

27848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00493

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00210

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000129

AC:

138

AN:

1069324

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

536282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000137

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00236

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000125

AC:

AN:

111856

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

52830

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00410

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000639

Hom.:

ExAC

AF:

0.000139

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 15, 2021

The c.785T>C (p.M262T) alteration is located in exon 7 (coding exon 5) of the TRIM49C gene. This alteration results from a T to C substitution at nucleotide position 785, causing the methionine (M) at amino acid position 262 to be replaced by a threonine (T). 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

0.34

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.1

DANN

Benign

0.24

DEOGEN2

Benign

0.046

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.0070

Sift

Benign

0.24

Sift4G

Benign

0.40

Polyphen

0.0020

Vest4

0.14

MutPred

0.45

Loss of catalytic residue at V258 (P = 0.0203);

MVP

0.030

MPC

1.9

ClinPred

0.029

GERP RS

-0.53

Varity_R

0.088

gMVP

0.032

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