Genetic Variant TRIM66:p.Arg1267Gln (chr11-8619483-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001388022.1(TRIM66):c.3800G>A(p.Arg1267Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000903 in 1,551,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

TRIM66
NM_001388022.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41197482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM66	NM_001388022.1 link	c.3800G>A	p.Arg1267Gln	missense_variant	Exon 23 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.3800G>A	p.Arg1267Gln	missense_variant	Exon 23 of 25		NM_001388022.1	ENSP00000495413.1		A0A8Z5E822

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

156200

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000166

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.00000786

AC:

AN:

1399006

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000834

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000371

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3272G>A (p.R1091Q) alteration is located in exon 18 (coding exon 17) of the TRIM66 gene. This alteration results from a G to A substitution at nucleotide position 3272, causing the arginine (R) at amino acid position 1091 to be replaced by a glutamine (Q). 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

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.035

T;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.4

N;N;.

REVEL

Benign

0.24

Sift

Uncertain

0.0050

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.36

MutPred

0.59

Loss of catalytic residue at R1091 (P = 0.021);.;.;

MVP

0.74

ClinPred

0.69

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.55

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