Genetic Variant TRIM48:p.Ser49Arg (chr11-55265002-C-G) – 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.147C>G(p.Ser49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,584,646 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00012 ( 21 hom. )

Consequence

TRIM48
NM_024114.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.228

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03686309).

BS2

High Homozygotes in GnomAdExome4 at 21 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.147C>G	p.Ser49Arg	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.147C>G	p.Ser49Arg	missense	Exon 2 of 6	ENSP00000402414.2	Q8IWZ4

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

147942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000683

Gnomad ASJ

AF:

0.00263

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0000448

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000180

AC:

AN:

244990

AF XY:

0.000212

show subpopulations

Gnomad AFR exome

AF:

0.000568

Gnomad AMR exome

AF:

0.0000884

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000981

Gnomad OTH exome

AF:

0.000501

GnomAD4 exome

AF:

0.000123

AC:

177

AN:

1436590

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

713690

show subpopulations

African (AFR)

AF:

0.000301

AC:

AN:

33168

American (AMR)

AF:

0.000137

AC:

AN:

43884

Ashkenazi Jewish (ASJ)

AF:

0.00306

AC:

AN:

25792

East Asian (EAS)

AF:

0.00

AC:

AN:

36822

South Asian (SAS)

AF:

0.00

AC:

AN:

79630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.000374

AC:

AN:

5348

European-Non Finnish (NFE)

AF:

0.0000500

AC:

AN:

1099450

Other (OTH)

AF:

0.000422

AC:

AN:

59270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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:

0.000230

AC:

AN:

148056

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

AN XY:

72122

show subpopulations

African (AFR)

AF:

0.000493

AC:

AN:

40532

American (AMR)

AF:

0.0000683

AC:

AN:

14650

Ashkenazi Jewish (ASJ)

AF:

0.00263

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

4612

South Asian (SAS)

AF:

0.00

AC:

AN:

4136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10490

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000448

AC:

AN:

66968

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.000294

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000151

AC:

EpiCase

AF:

0.000110

EpiControl

AF:

0.000120

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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.19

M_CAP

Benign

0.0012

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

PhyloP100

0.23

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.15

Sift

Uncertain

0.018

Sift4G

Uncertain

0.029

Vest4

0.27

MVP

0.25

MPC

0.0073

ClinPred

0.087

GERP RS

-1.2

gMVP

0.065

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