Genetic Variant TRIM49C:p.Gln119Leu (chr11-90035567-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001195234.1(TRIM49C):c.356A>T(p.Gln119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000032 in 1,344,670 control chromosomes in the GnomAD database, including 2 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 0.000064 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000032 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49C
NM_001195234.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.18

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052271634).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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.356A>T	p.Gln119Leu	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.356A>T	p.Gln119Leu	missense	Exon 3 of 8	ENSP00000388299.1	P0CI26

Frequencies

GnomAD3 genomes

AF:

0.0000636

AC:

AN:

110126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000108

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:

0.0000361

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000495

AC:

AN:

181772

AF XY:

0.0000399

show subpopulations

Gnomad AFR exome

AF:

0.000211

Gnomad AMR exome

AF:

0.0000496

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000677

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000114

Gnomad OTH exome

AF:

0.000210

GnomAD4 exome

AF:

0.0000320

AC:

AN:

1344670

Hom.:

Cov.:

AF XY:

0.0000314

AC XY:

AN XY:

669524

show subpopulations

African (AFR)

AF:

0.0000670

AC:

AN:

29838

American (AMR)

AF:

0.0000299

AC:

AN:

33440

Ashkenazi Jewish (ASJ)

AF:

0.0000808

AC:

AN:

24744

East Asian (EAS)

AF:

0.00

AC:

AN:

37392

South Asian (SAS)

AF:

0.0000899

AC:

AN:

77834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46914

Middle Eastern (MID)

AF:

0.000254

AC:

AN:

3936

European-Non Finnish (NFE)

AF:

0.0000232

AC:

AN:

1034234

Other (OTH)

AF:

0.000107

AC:

AN:

56338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000636

AC:

AN:

110126

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

51854

show subpopulations

African (AFR)

AF:

0.000146

AC:

AN:

27450

American (AMR)

AF:

0.000108

AC:

AN:

9290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2898

East Asian (EAS)

AF:

0.00

AC:

AN:

3786

South Asian (SAS)

AF:

0.00

AC:

AN:

2824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0000361

AC:

AN:

55330

Other (OTH)

AF:

0.00

AC:

AN:

1482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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:

0.0000843

Hom.:

ExAC

AF:

0.0000296

AC:

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

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.047

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.39

M_CAP

Benign

0.0029

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.9

PhyloP100

-5.2

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.11

Sift

Benign

0.11

Sift4G

Benign

0.14

Polyphen

0.064

Vest4

0.096

MutPred

0.54

Gain of helix (P = 0.0696)

MVP

0.19

MPC

1.8

ClinPred

0.057

GERP RS

-0.85

Varity_R

0.17

gMVP

0.075

Mutation Taster

=100/0

polymorphism

(source)

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

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