Variant 11-90035539-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000448984.1(TRIM49C):c.328C>A(p.Leu110Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 17)

Exomes 𝑓: 0.000027 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49C
ENST00000448984.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.10

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29985988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49C	NM_001195234.1 linkuse as main transcript	c.328C>A	p.Leu110Met	missense_variant	3/8	ENST00000448984.1	NP_001182163.1	P0CI26
TRIM49C	XM_024448656.2 linkuse as main transcript	c.328C>A	p.Leu110Met	missense_variant	1/6		XP_024304424.1
TRIM49C	XM_017018126.2 linkuse as main transcript	c.328C>A	p.Leu110Met	missense_variant	1/5		XP_016873615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49C	ENST00000448984.1 linkuse as main transcript	c.328C>A	p.Leu110Met	missense_variant	3/8	1	NM_001195234.1	ENSP00000388299.1		P0CI26

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000600

AC:

AN:

166546

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

91538

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:

0.0000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000265

AC:

AN:

1357792

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

675430

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:

0.0000316

Gnomad4 OTH exome

AF:

0.0000527

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000199

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

Jun 13, 2023

The c.328C>A (p.L110M) alteration is located in exon 3 (coding exon 1) of the TRIM49C gene. This alteration results from a C to A substitution at nucleotide position 328, causing the leucine (L) at amino acid position 110 to be replaced by a methionine (M). 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

0.22

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.80

M_CAP

Benign

0.0015

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Polyphen

0.99

Vest4

0.26

MutPred

0.64

Gain of catalytic residue at L110 (P = 0.0191);

MVP

0.34

MPC

3.0

ClinPred

0.58

GERP RS

0.73

Varity_R

0.18

gMVP

0.023

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