Genetic Variant TRIM66:p.His469Arg (chr11-8640969-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001388022.1(TRIM66):c.1406A>G(p.His469Arg) variant causes a missense change. The variant allele was found at a frequency of 0.629 in 1,550,904 control chromosomes in the GnomAD database, including 310,086 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 27100 hom., cov: 30)

Exomes 𝑓: 0.63 ( 282986 hom. )

Consequence

TRIM66
NM_001388022.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.49

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.3181745E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM66	NM_001388022.1 link	c.1406A>G	p.His469Arg	missense_variant	Exon 14 of 25	ENST00000646038.2	NP_001374951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM66	ENST00000646038.2 link	c.1406A>G	p.His469Arg	missense_variant	Exon 14 of 25		NM_001388022.1	ENSP00000495413.1		A0A8Z5E822

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

89991

AN:

151736

Hom.:

27078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.605

Gnomad NFE

AF:

0.647

Gnomad OTH

AF:

0.586

GnomAD3 exomes

AF:

0.597

AC:

92770

AN:

155268

Hom.:

28216

AF XY:

0.597

AC XY:

49149

AN XY:

82360

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.567

Gnomad ASJ exome

AF:

0.630

Gnomad EAS exome

AF:

0.405

Gnomad SAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.665

Gnomad NFE exome

AF:

0.648

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.633

AC:

885558

AN:

1399052

Hom.:

282986

Cov.:

AF XY:

0.631

AC XY:

435089

AN XY:

690014

show subpopulations

Gnomad4 AFR exome

AF:

0.514

Gnomad4 AMR exome

AF:

0.572

Gnomad4 ASJ exome

AF:

0.625

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.557

Gnomad4 FIN exome

AF:

0.663

Gnomad4 NFE exome

AF:

0.652

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.593

AC:

90053

AN:

151852

Hom.:

27100

Cov.:

AF XY:

0.592

AC XY:

43925

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.563

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.401

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.661

Gnomad4 NFE

AF:

0.647

Gnomad4 OTH

AF:

0.589

Alfa

AF:

0.625

Hom.:

71791

Bravo

AF:

0.583

TwinsUK

AF:

0.650

AC:

2410

ALSPAC

AF:

0.667

AC:

2571

ESP6500AA

AF:

0.534

AC:

739

ESP6500EA

AF:

0.657

AC:

2089

ExAC

AF:

0.551

AC:

14393

Asia WGS

AF:

0.485

AC:

1689

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.000083

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.3

D;D;.

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.022

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.40

ClinPred

0.014

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.66

gMVP

0.64

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over