Genetic Variant TRIM49C:p.Met92Leu (chr11-90035485-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195234.1(TRIM49C):c.274A>C(p.Met92Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000337 in 1,481,954 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000081 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000029 ( 1 hom. )

Consequence

TRIM49C
NM_001195234.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.46

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11628458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195234.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49C	NM_001195234.1	MANE Select	c.274A>C	p.Met92Leu	missense	Exon 3 of 8	NP_001182163.1	P0CI26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49C	ENST00000448984.1	TSL:1 MANE Select	c.274A>C	p.Met92Leu	missense	Exon 3 of 8	ENSP00000388299.1	P0CI26

Frequencies

GnomAD3 genomes

AF:

0.00000806

AC:

AN:

124086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000305

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

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1357868

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

674900

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31322

American (AMR)

AF:

0.00

AC:

AN:

32208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24952

East Asian (EAS)

AF:

0.00

AC:

AN:

37438

South Asian (SAS)

AF:

0.00

AC:

AN:

79084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4020

European-Non Finnish (NFE)

AF:

0.00000383

AC:

AN:

1045164

Other (OTH)

AF:

0.00

AC:

AN:

56826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000806

AC:

AN:

124086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

59288

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32814

American (AMR)

AF:

0.00

AC:

AN:

10664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3180

East Asian (EAS)

AF:

0.00

AC:

AN:

4158

South Asian (SAS)

AF:

0.00

AC:

AN:

3358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59610

Other (OTH)

AF:

0.00

AC:

AN:

1680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.21

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.063

M_CAP

Benign

0.0017

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.36

PhyloP100

-2.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.98

REVEL

Benign

0.031

Sift

Benign

0.24

Sift4G

Benign

0.42

Polyphen

0.0050

Vest4

0.12

MutPred

0.60

Loss of phosphorylation at T95 (P = 0.1416)

MVP

0.088

MPC

1.6

ClinPred

0.047

GERP RS

-0.56

Varity_R

0.21

gMVP

0.029

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over