chr11-8640969-T-C

Variant names:

• chr11-8640969-T-C
• rs11042023
• NM_001388022.1:c.1406A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• Publications: 61 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	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	c.1406A>G	p.His469Arg	missense_variant	Exon 14 of 25		NM_001388022.1	ENSP00000495413.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89991 AN: 151736 Hom.: 27078 Cov.: 30

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

GnomAD2 exomes AF: 0.597 AC: 92770 AN: 155268 AF XY: 0.597

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 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.: 79 AF XY: 0.631 AC XY: 435089 AN XY: 690014

African (AFR) AF: 0.514 AC: 16246 AN: 31586

American (AMR) AF: 0.572 AC: 20433 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 15730 AN: 25180

East Asian (EAS) AF: 0.381 AC: 13621 AN: 35738

South Asian (SAS) AF: 0.557 AC: 44144 AN: 79218

European-Finnish (FIN) AF: 0.663 AC: 32662 AN: 49270

Middle Eastern (MID) AF: 0.584 AC: 3169 AN: 5428

European-Non Finnish (NFE) AF: 0.652 AC: 703904 AN: 1078956

Other (OTH) AF: 0.615 AC: 35649 AN: 57972

GnomAD4 genome AF: 0.593 AC: 90053 AN: 151852 Hom.: 27100 Cov.: 30 AF XY: 0.592 AC XY: 43925 AN XY: 74182

African (AFR) AF: 0.523 AC: 21670 AN: 41410

American (AMR) AF: 0.563 AC: 8609 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2174 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2058 AN: 5128

South Asian (SAS) AF: 0.536 AC: 2571 AN: 4800

European-Finnish (FIN) AF: 0.661 AC: 6984 AN: 10558

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.647 AC: 43960 AN: 67904

Other (OTH) AF: 0.589 AC: 1239 AN: 2104

Alfa AF: 0.622 Hom.: 130685

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	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T;T;T
MetaRNN	Benign	0.000083	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;.;.
PhyloP100		5.5
PrimateAI	Uncertain	0.54	T
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	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.64
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11042023; hg19: chr11-8662516; COSMIC: COSV55124735; COSMIC: COSV55124735;