Genetic Variant TRIM48:p.Leu98Ile (chr11-55265147-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_024114.5(TRIM48):c.292C>A(p.Leu98Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,582,598 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000061 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00011 ( 17 hom. )

Consequence

TRIM48
NM_024114.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500

Publications

0 publications found

Variant links:

Genes affected

TRIM48 (HGNC:19021): (tripartite motif containing 48) 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]

TRIM48 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=0.04185316).

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024114.5. 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
	TRIM48	NM_024114.5	MANE Select	c.292C>A	p.Leu98Ile	missense	Exon 2 of 6	NP_077019.2	Q8IWZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM48	ENST00000417545.5	TSL:1 MANE Select	c.292C>A	p.Leu98Ile	missense	Exon 2 of 6	ENSP00000402414.2	Q8IWZ4

Frequencies

GnomAD3 genomes

AF:

0.0000608

AC:

AN:

148014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000682

Gnomad ASJ

AF:

0.000292

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0131

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.000990

GnomAD2 exomes

AF:

0.000208

AC:

AN:

245244

AF XY:

0.000212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000766

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.0000577

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000107

AC:

154

AN:

1434472

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

712528

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33106

American (AMR)

AF:

0.000661

AC:

AN:

43866

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

25768

East Asian (EAS)

AF:

0.0000272

AC:

AN:

36762

South Asian (SAS)

AF:

0.00

AC:

AN:

79528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53214

Middle Eastern (MID)

AF:

0.00148

AC:

AN:

4066

European-Non Finnish (NFE)

AF:

0.0000601

AC:

AN:

1099064

Other (OTH)

AF:

0.000338

AC:

AN:

59098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

0.0000608

AC:

AN:

148126

Hom.:

Cov.:

AF XY:

0.0000692

AC XY:

AN XY:

72212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40644

American (AMR)

AF:

0.0000681

AC:

AN:

14674

Ashkenazi Jewish (ASJ)

AF:

0.000292

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

4624

South Asian (SAS)

AF:

0.00

AC:

AN:

4122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10474

Middle Eastern (MID)

AF:

0.0141

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

66928

Other (OTH)

AF:

0.000979

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000170

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.000143

AC:

EpiCase

AF:

0.000221

EpiControl

AF:

0.000180

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

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.0042

M_CAP

Benign

0.0043

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.66

PhyloP100

0.050

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

REVEL

Benign

0.25

Sift

Benign

0.16

Sift4G

Benign

0.40

Vest4

0.17

MVP

0.49

MPC

0.0037

ClinPred

0.081

GERP RS

0.60

gMVP

0.012

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