Variant chr4-188091681-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173553.4(TRIML2):c.1006G>A(p.Gly336Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TRIML2
NM_173553.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.961

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.072306484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIML2	NM_173553.4 linkuse as main transcript	c.1006G>A	p.Gly336Arg	missense_variant	8/8	ENST00000682553.1	NP_775824.2	Q8N7C3-1A0A804HJA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIML2	ENST00000682553.1 linkuse as main transcript	c.1006G>A	p.Gly336Arg	missense_variant	8/8		NM_173553.4	ENSP00000507413.1		Q8N7C3-1A0A804HJA0

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251236

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460804

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726460

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2024

The c.856G>A (p.G286R) alteration is located in exon 7 (coding exon 7) of the TRIML2 gene. This alteration results from a G to A substitution at nucleotide position 856, causing the glycine (G) at amino acid position 286 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.9

DANN

Benign

0.86

DEOGEN2

Benign

0.088

.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

REVEL

Benign

0.11

Sift4G

Benign

0.18

T;T

Vest4

0.093

MVP

0.26

MPC

0.11

ClinPred

0.19

GERP RS

0.92

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over