Variant 11-90035976-G-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 ENST00000448984.1(TRIM49C):c.500G>T(p.Cys167Phe) 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 0.000013 ( 0 hom., cov: 9)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

TRIM49C
ENST00000448984.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.83

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07358393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49C	NM_001195234.1 linkuse as main transcript	c.500G>T	p.Cys167Phe	missense_variant	4/8	ENST00000448984.1	NP_001182163.1	P0CI26
TRIM49C	XM_024448656.2 linkuse as main transcript	c.500G>T	p.Cys167Phe	missense_variant	2/6		XP_024304424.1
TRIM49C	XM_017018126.2 linkuse as main transcript	c.500G>T	p.Cys167Phe	missense_variant	2/5		XP_016873615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49C	ENST00000448984.1 linkuse as main transcript	c.500G>T	p.Cys167Phe	missense_variant	4/8	1	NM_001195234.1	ENSP00000388299.1		P0CI26

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

74526

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00109

GnomAD3 exomes

AF:

0.0000305

AC:

AN:

65470

Hom.:

AF XY:

0.0000620

AC XY:

AN XY:

32284

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000721

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000809

AC:

AN:

742032

Hom.:

Cov.:

AF XY:

0.00000806

AC XY:

AN XY:

372330

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000106

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000134

AC:

AN:

74526

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34932

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00109

ExAC

AF:

0.0000355

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

Oct 05, 2021

The c.500G>T (p.C167F) alteration is located in exon 4 (coding exon 2) of the TRIM49C gene. This alteration results from a G to T substitution at nucleotide position 500, causing the cysteine (C) at amino acid position 167 to be replaced by a phenylalanine (F). 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

-0.52

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0070

DANN

Benign

0.23

DEOGEN2

Benign

0.032

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.00067

LIST_S2

Benign

0.19

M_CAP

Benign

0.00063

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.92

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.88

REVEL

Benign

0.018

Sift

Benign

0.70

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.11

MutPred

0.47

Loss of catalytic residue at W168 (P = 5e-04);

MVP

0.030

MPC

2.3

ClinPred

0.028

GERP RS

-1.8

Varity_R

0.042

gMVP

0.027

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