Genetic Variant TRIML2:p.Val184Ile (chr4-188099106-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173553.4(TRIML2):c.550G>A(p.Val184Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,614,100 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 123 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 118 hom. )

Consequence

TRIML2
NM_173553.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.107

Publications

4 publications found

Variant links:

Genes affected

TRIML2 (HGNC:26378): (tripartite motif family like 2) This gene encodes a member of the tri-partite motif (TRIM) family of proteins. This protein may be regulated by the tumor suppressor p53 and may regulate p53 through the enhancement of p53 SUMOylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

TRIML2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017769635).

BP6

Variant 4-188099106-C-T is Benign according to our data. Variant chr4-188099106-C-T is described in ClinVar as Benign. ClinVar VariationId is 780938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173553.4. 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
	TRIML2	NM_173553.4	MANE Select	c.550G>A	p.Val184Ile	missense	Exon 5 of 8	NP_775824.2	Q8N7C3-1
	TRIML2	NM_001303419.1		c.550G>A	p.Val184Ile	missense	Exon 4 of 8	NP_001290348.1	B7ZLC3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIML2	ENST00000682553.1	MANE Select	c.550G>A	p.Val184Ile	missense	Exon 5 of 8	ENSP00000507413.1	Q8N7C3-1
TRIML2	ENST00000512729.5	TSL:1	c.550G>A	p.Val184Ile	missense	Exon 4 of 7	ENSP00000422581.2	Q8N7C3-1
TRIML2	ENST00000326754.7	TSL:1	c.430G>A	p.Val144Ile	missense	Exon 4 of 8	ENSP00000317498.4	J3KNI5

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3491

AN:

152132

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0791

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00600

AC:

1508

AN:

251368

AF XY:

0.00437

show subpopulations

Gnomad AFR exome

AF:

0.0779

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00247

AC:

3610

AN:

1461850

Hom.:

118

Cov.:

AF XY:

0.00210

AC XY:

1526

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0800

AC:

2679

AN:

33476

American (AMR)

AF:

0.00512

AC:

229

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000324

AC:

360

AN:

1111992

Other (OTH)

AF:

0.00492

AC:

297

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

177

354

530

707

884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0230

AC:

3505

AN:

152250

Hom.:

123

Cov.:

AF XY:

0.0224

AC XY:

1667

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0792

AC:

3287

AN:

41516

American (AMR)

AF:

0.0102

AC:

156

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68012

Other (OTH)

AF:

0.0132

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

159

319

478

638

797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00852

Hom.:

Bravo

AF:

0.0261

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0751

AC:

331

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00735

AC:

892

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000655

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.11

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

PhyloP100

-0.11

PrimateAI

Benign

0.39

REVEL

Benign

0.010

Sift4G

Benign

1.0

Vest4

0.027

MVP

0.014

MPC

0.061

ClinPred

0.00056

GERP RS

1.1

gMVP

0.051

Mutation Taster

=99/1

polymorphism (auto)

(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