Variant 11-8620481-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001388022.1(TRIM66):c.3637C>T(p.Arg1213Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,551,766 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 26 hom. )

Consequence

TRIM66
NM_001388022.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.884

Variant links:

Genes affected

TRIM66 (HGNC:29005): (tripartite motif containing 66) Predicted to enable chromatin binding activity and identical protein binding activity. Predicted to act upstream of or within negative regulation of transcription, DNA-templated. Located in aggresome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM66 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055477023).

BP6

Variant 11-8620481-G-A is Benign according to our data. Variant chr11-8620481-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641581.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM66	NM_001388022.1 link	c.3637C>T	p.Arg1213Trp	missense_variant	21/25	ENST00000646038.2	NP_001374951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM66	ENST00000646038.2 link	c.3637C>T	p.Arg1213Trp	missense_variant	21/25		NM_001388022.1	ENSP00000495413.1		A0A8Z5E822

Frequencies

GnomAD3 genomes

AF:

0.00323

AC:

491

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00472

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00398

AC:

621

AN:

155946

Hom.:

AF XY:

0.00446

AC XY:

368

AN XY:

82602

show subpopulations

Gnomad AFR exome

AF:

0.000504

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00747

Gnomad FIN exome

AF:

0.00220

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.00435

GnomAD4 exome

AF:

0.00472

AC:

6610

AN:

1399430

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

3303

AN XY:

690216

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00682

Gnomad4 FIN exome

AF:

0.00235

Gnomad4 NFE exome

AF:

0.00502

Gnomad4 OTH exome

AF:

0.00467

GnomAD4 genome

AF:

0.00322

AC:

490

AN:

152336

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00472

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00289

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00503

AC:

ExAC

AF:

0.00370

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

TRIM66: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.1

D;D;.

REVEL

Benign

0.079

Sift

Uncertain

0.0010

D;D;.

Sift4G

Uncertain

0.018

D;T;.

Polyphen

0.081

B;.;.

Vest4

0.22

MVP

0.73

ClinPred

0.031

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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