Variant 11-8621264-C-A 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_001388022.1(TRIM66):c.3313G>T(p.Val1105Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TRIM66
NM_001388022.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.807

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:

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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=0.12293947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM66	NM_001388022.1 linkuse as main transcript	c.3313G>T	p.Val1105Phe	missense_variant	20/25	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.3313G>T	p.Val1105Phe	missense_variant	20/25		NM_001388022.1	ENSP00000495413	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000647

AC:

AN:

154624

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82044

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000918

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:

7.15e-7

AC:

AN:

1399398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 20, 2024

The c.2785G>T (p.V929F) alteration is located in exon 15 (coding exon 14) of the TRIM66 gene. This alteration results from a G to T substitution at nucleotide position 2785, causing the valine (V) at amino acid position 929 to be replaced by a phenylalanine (F). 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

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0024

T;.;.

Eigen

Benign

-0.023

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.80

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.064

Sift

Benign

0.21

T;T;.

Sift4G

Benign

0.69

T;T;.

Polyphen

0.029

B;.;.

Vest4

0.19

MutPred

0.14

Gain of catalytic residue at V929 (P = 0.1058);.;.;

MVP

0.45

ClinPred

0.52

GERP RS

5.2

Varity_R

0.11

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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