11-8620069-T-C

Variant summary

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

The NM_001388022.1(TRIM66):​c.3728A>G​(p.His1243Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,452 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: not found (cov: 33)
Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

TRIM66
NM_001388022.1 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98
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]

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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=0.4228195).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM66NM_001388022.1 linkc.3728A>G p.His1243Arg missense_variant Exon 22 of 25 ENST00000646038.2 NP_001374951.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM66ENST00000646038.2 linkc.3728A>G p.His1243Arg missense_variant Exon 22 of 25 NM_001388022.1 ENSP00000495413.1 A0A8Z5E822

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000357
AC:
5
AN:
1399452
Hom.:
0
Cov.:
32
AF XY:
0.00000580
AC XY:
4
AN XY:
690240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000252
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3200A>G (p.H1067R) alteration is located in exon 17 (coding exon 16) of the TRIM66 gene. This alteration results from a A to G substitution at nucleotide position 3200, causing the histidine (H) at amino acid position 1067 to be replaced by an arginine (R). 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
Pathogenic
0.68
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.033
T;.;.
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D;T;D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.42
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.34
N;.;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-2.4
N;N;.
REVEL
Uncertain
0.30
Sift
Benign
0.12
T;T;.
Sift4G
Uncertain
0.0090
D;D;.
Polyphen
0.58
P;.;.
Vest4
0.44
MutPred
0.50
Gain of loop (P = 0.1069);.;.;
MVP
0.47
ClinPred
0.86
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.40
gMVP
0.58

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.

Other links and lift over

dbSNP: rs2034059727; hg19: chr11-8641616; API