rs976067522

Variant names:

• chr11-8618902-T-C
• rs976067522
• NM_001388022.1:c.3967A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001388022.1(TRIM66):​c.3967A>G​(p.Ile1323Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,399,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000014 (0 hom.)
• Consequence: TRIM66 NM_001388022.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13278696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388022.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM66	NM_001388022.1	MANE Select	c.3967A>G	p.Ile1323Val	missense	Exon 24 of 25	NP_001374951.1	A0A8Z5E822
	TRIM66	NM_001388024.1		c.3883A>G	p.Ile1295Val	missense	Exon 25 of 26	NP_001374953.1
	TRIM66	NM_001388023.1		c.3856A>G	p.Ile1286Val	missense	Exon 24 of 25	NP_001374952.1	A0A994J572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM66	ENST00000646038.2	MANE Select	c.3967A>G	p.Ile1323Val	missense	Exon 24 of 25	ENSP00000495413.1	A0A8Z5E822
	TRIM66	ENST00000705689.1		c.3856A>G	p.Ile1286Val	missense	Exon 24 of 25	ENSP00000516162.1	A0A994J572
	TRIM66	ENST00000705690.1		c.3532A>G	p.Ile1178Val	missense	Exon 19 of 20	ENSP00000516163.1	A0A994J7V7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 155740 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000184

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000136 AC: 19 AN: 1399292 Hom.: 0 Cov.: 31 AF XY: 0.0000130 AC XY: 9 AN XY: 690134

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.000504 AC: 18 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078972

Other (OTH) AF: 0.0000172 AC: 1 AN: 58006

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.076
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.045
Sift	Benign	0.086	T
Sift4G	Benign	0.66	T
Polyphen		0.21	B
Vest4		0.12
MutPred		0.38		Loss of catalytic residue at P1149 (P = 0.0306)
MVP		0.45
ClinPred		0.26	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.15
Mutation Taster		=86/14	polymorphism

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: rs976067522; hg19: chr11-8640449;