Variant 11-8620456-T-C 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.3662A>G(p.Tyr1221Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,551,754 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 15 hom. )

Consequence

TRIM66
NM_001388022.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.332

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=0.006609887).

BP6

Variant 11-8620456-T-C is Benign according to our data. Variant chr11-8620456-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 711377.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM66	NM_001388022.1 linkuse as main transcript	c.3662A>G	p.Tyr1221Cys	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 linkuse as main transcript	c.3662A>G	p.Tyr1221Cys	missense_variant	21/25		NM_001388022.1	ENSP00000495413	P1

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00219

AC:

341

AN:

155992

Hom.:

AF XY:

0.00254

AC XY:

210

AN XY:

82624

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00597

Gnomad FIN exome

AF:

0.00131

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00297

AC:

4154

AN:

1399396

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

2120

AN XY:

690202

show subpopulations

Gnomad4 AFR exome

AF:

0.000285

Gnomad4 AMR exome

AF:

0.00160

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00605

Gnomad4 FIN exome

AF:

0.00164

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00138

AC:

211

AN:

152358

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00174

Hom.:

Bravo

AF:

0.00135

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00283

AC:

ExAC

AF:

0.00291

AC:

Asia WGS

AF:

0.00231

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

Labcorp Genetics (formerly Invitae), Labcorp

Apr 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.6

DANN

Benign

0.87

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.82

L;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.9

D;D;.

REVEL

Benign

0.016

Sift

Benign

0.12

T;T;.

Sift4G

Benign

0.22

T;T;.

Polyphen

0.0

B;.;.

Vest4

0.15

MVP

0.46

ClinPred

0.0053

GERP RS

-0.58

Varity_R

0.37

gMVP

0.35

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