Genetic Variant TRIML2:p.Arg164His (chr4-188099165-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_173553.4(TRIML2):c.491G>A(p.Arg164His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,608,396 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

TRIML2
NM_173553.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

Publications

5 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013650864).

BP6

Variant 4-188099165-C-T is Benign according to our data. Variant chr4-188099165-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2292054.Status of the report is criteria_provided_single_submitter, 1 stars.

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.491G>A	p.Arg164His	missense	Exon 5 of 8	NP_775824.2	Q8N7C3-1
	TRIML2	NM_001303419.1		c.491G>A	p.Arg164His	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.491G>A	p.Arg164His	missense	Exon 5 of 8	ENSP00000507413.1	Q8N7C3-1
TRIML2	ENST00000512729.5	TSL:1	c.491G>A	p.Arg164His	missense	Exon 4 of 7	ENSP00000422581.2	Q8N7C3-1
TRIML2	ENST00000326754.7	TSL:1	c.371G>A	p.Arg124His	missense	Exon 4 of 8	ENSP00000317498.4	J3KNI5

Frequencies

GnomAD3 genomes

AF:

0.000696

AC:

106

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00134

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000682

AC:

167

AN:

244970

AF XY:

0.000642

show subpopulations

Gnomad AFR exome

AF:

0.000434

Gnomad AMR exome

AF:

0.000518

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.000504

GnomAD4 exome

AF:

0.00121

AC:

1758

AN:

1456088

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

809

AN XY:

724094

show subpopulations

African (AFR)

AF:

0.000181

AC:

AN:

33108

American (AMR)

AF:

0.000416

AC:

AN:

43280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25772

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39602

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84910

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00152

AC:

1682

AN:

1110210

Other (OTH)

AF:

0.000682

AC:

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

168

252

336

420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.000696

AC:

106

AN:

152308

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41576

American (AMR)

AF:

0.000262

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00134

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

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

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:

0.00112

Hom.:

Bravo

AF:

0.000691

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000692

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.000890

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.073

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0060

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0099

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.15

M_CAP

Benign

0.0064

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

PhyloP100

-1.7

PrimateAI

Benign

0.24

REVEL

Benign

0.010

Sift4G

Benign

0.63

Vest4

0.078

MVP

0.072

MPC

0.091

ClinPred

0.0028

GERP RS

-7.9

gMVP

0.055

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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