Genetic Variant TRIML2:p.Leu367Leu (chr4-188091588-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_173553.4(TRIML2):c.1099T>C(p.Leu367Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,614,134 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 37 hom. )

Consequence

TRIML2
NM_173553.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.16

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-188091588-A-G is Benign according to our data. Variant chr4-188091588-A-G is described in ClinVar as [Benign]. Clinvar id is 721051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.16 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIML2	NM_173553.4 link	c.1099T>C	p.Leu367Leu	synonymous_variant	Exon 8 of 8	ENST00000682553.1	NP_775824.2	Q8N7C3-1A0A804HJA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIML2	ENST00000682553.1 link	c.1099T>C	p.Leu367Leu	synonymous_variant	Exon 8 of 8		NM_173553.4	ENSP00000507413.1		Q8N7C3-1A0A804HJA0

Frequencies

GnomAD3 genomes

AF:

0.00461

AC:

701

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00619

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00472

AC:

1187

AN:

251438

AF XY:

0.00486

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0233

Gnomad NFE exome

AF:

0.00520

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00423

AC:

6188

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

3090

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.000581

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00505

AC:

132

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0226

AC:

1208

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00414

AC:

4600

AN:

1112000

Other (OTH)

AF:

0.00330

AC:

199

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

416

832

1247

1663

2079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00460

AC:

701

AN:

152258

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

384

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41548

American (AMR)

AF:

0.00157

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0213

AC:

226

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00619

AC:

421

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00648

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.46

(source)

DANN

Benign

0.38

PhyloP100

1.2

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

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4-188091588-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over