Genetic Variant TRIM49C:p.Arg122Trp (chr11-90035575-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001195234.1(TRIM49C):c.364C>T(p.Arg122Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000016 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49C
NM_001195234.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

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=0.15788192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM49C	NM_001195234.1 link	c.364C>T	p.Arg122Trp	missense_variant	Exon 3 of 8	ENST00000448984.1	NP_001182163.1	P0CI26
TRIM49C	XM_024448656.2 link	c.364C>T	p.Arg122Trp	missense_variant	Exon 1 of 6		XP_024304424.1
TRIM49C	XM_017018126.2 link	c.364C>T	p.Arg122Trp	missense_variant	Exon 1 of 5		XP_016873615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM49C	ENST00000448984.1 link	c.364C>T	p.Arg122Trp	missense_variant	Exon 3 of 8	1	NM_001195234.1	ENSP00000388299.1		P0CI26

Frequencies

GnomAD3 genomes

AF:

0.0000275

AC:

AN:

109268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000112

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:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182720

Hom.:

AF XY:

0.00000992

AC XY:

AN XY:

100794

show subpopulations

Gnomad AFR exome

AF:

0.000105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000947

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000164

AC:

AN:

1338750

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

666760

show subpopulations

Gnomad4 AFR exome

AF:

0.0000678

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000168

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000680

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000275

AC:

AN:

109268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

51490

show subpopulations

Gnomad4 AFR

AF:

0.000112

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:

0.00

Alfa

AF:

0.000169

Hom.:

ExAC

AF:

0.0000197

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.364C>T (p.R122W) alteration is located in exon 3 (coding exon 1) of the TRIM49C gene. This alteration results from a C to T substitution at nucleotide position 364, causing the arginine (R) at amino acid position 122 to be replaced by a tryptophan (W). 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

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.087

M_CAP

Benign

0.0024

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.055

Sift

Uncertain

0.016

Sift4G

Uncertain

0.018

Polyphen

0.73

Vest4

0.18

MutPred

0.63

Loss of disorder (P = 0.0104);

MVP

0.27

MPC

2.2

ClinPred

0.25

GERP RS

-0.50

Varity_R

0.061

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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