Genetic Variant TRIML1:p.Thr286Lys (chr4-188146822-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178556.5(TRIML1):c.857C>A(p.Thr286Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIML1
NM_178556.5 missense, splice_region

Scores

Splicing: ADA: 0.0003518

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11

Publications

1 publications found

Variant links:

Genes affected

TRIML1 (HGNC:26698): (tripartite motif family like 1) The protein encoded by this gene is a tripartite motif family protein with similarities to E3 ubiquitin-protein ligases. While the function of the encoded protein has not been determined, the orthologous protein in mouse has been shown to bind ubiquitin-specific protease 5 and is involved in the blastocyst development stage. [provided by RefSeq, Sep 2016]

TRIML1 links:

ENSG00000247130 (HGNC:):

ENSG00000247130 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18764374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178556.5. 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
	TRIML1	NM_178556.5	MANE Select	c.857C>A	p.Thr286Lys	missense splice_region	Exon 6 of 6	NP_848651.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIML1	ENST00000332517.4	TSL:1 MANE Select	c.857C>A	p.Thr286Lys	missense splice_region	Exon 6 of 6	ENSP00000327738.3	Q8N9V2
TRIML1	ENST00000507581.5	TSL:1	n.317C>A		splice_region non_coding_transcript_exon	Exon 3 of 3
TRIML1	ENST00000512233.1	TSL:3	n.207C>A		splice_region non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1205434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

579396

African (AFR)

AF:

0.00

AC:

AN:

26150

American (AMR)

AF:

0.00

AC:

AN:

19156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16440

East Asian (EAS)

AF:

0.00

AC:

AN:

32096

South Asian (SAS)

AF:

0.00

AC:

AN:

34244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4804

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

980720

Other (OTH)

AF:

0.00

AC:

AN:

48794

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

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

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0096

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.20

M_CAP

Benign

0.021

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.73

PhyloP100

-1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.070

REVEL

Benign

0.14

Sift

Benign

0.25

Sift4G

Benign

0.93

Polyphen

0.22

Vest4

0.52

MutPred

0.57

Gain of ubiquitination at T286 (P = 0.0247)

MVP

0.26

MPC

0.061

ClinPred

0.23

GERP RS

4.0

Varity_R

0.12

gMVP

0.48

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00035

dbscSNV1_RF

Benign

0.042

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over