Genetic Variant TRIM49C:p.Lys79Arg (chr11-90035447-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001195234.1(TRIM49C):c.236A>G(p.Lys79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000045 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49C
NM_001195234.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.477

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06553918).

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.236A>G	p.Lys79Arg	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.236A>G	p.Lys79Arg	missense	Exon 3 of 8	ENSP00000388299.1	P0CI26

Frequencies

GnomAD3 genomes

AF:

0.0000155

AC:

AN:

129096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000289

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:

0.0000163

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000204

AC:

AN:

196492

AF XY:

0.0000374

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000332

Gnomad OTH exome

AF:

0.000194

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000449

AC:

AN:

1358332

Hom.:

Cov.:

AF XY:

0.0000503

AC XY:

AN XY:

675600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31384

American (AMR)

AF:

0.00

AC:

AN:

32396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24968

East Asian (EAS)

AF:

0.00

AC:

AN:

37114

South Asian (SAS)

AF:

0.00

AC:

AN:

79606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4490

European-Non Finnish (NFE)

AF:

0.0000555

AC:

AN:

1045134

Other (OTH)

AF:

0.0000529

AC:

AN:

56742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000155

AC:

AN:

129096

Hom.:

Cov.:

AF XY:

0.0000322

AC XY:

AN XY:

62034

show subpopulations

African (AFR)

AF:

0.0000289

AC:

AN:

34614

American (AMR)

AF:

0.00

AC:

AN:

11280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3252

East Asian (EAS)

AF:

0.00

AC:

AN:

4324

South Asian (SAS)

AF:

0.00

AC:

AN:

3614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000163

AC:

AN:

61176

Other (OTH)

AF:

0.00

AC:

AN:

1754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000712

Hom.:

ExAC

AF:

0.0000185

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

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.025

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0055

LIST_S2

Benign

0.61

M_CAP

Benign

0.0055

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.9

PhyloP100

-0.48

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

REVEL

Benign

0.095

Sift

Benign

0.14

Sift4G

Benign

0.30

Polyphen

0.30

Vest4

0.061

MutPred

0.33

Loss of ubiquitination at K79 (P = 0.0362)

MVP

0.27

MPC

1.5

ClinPred

0.037

GERP RS

-0.55

Varity_R

0.035

gMVP

0.026

Mutation Taster

=99/1

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