rs1460524698

Variant names:

• chr11-8618940-C-A
• rs1460524698
• NM_001388022.1:c.3929G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-8618940-C-A
• chr11-8618940-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001388022.1(TRIM66):​c.3929G>T​(p.Arg1310Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,399,268 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: 31)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: TRIM66 NM_001388022.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40301335).

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.3929G>T	p.Arg1310Leu	missense	Exon 24 of 25	NP_001374951.1	A0A8Z5E822
	TRIM66	NM_001388024.1		c.3845G>T	p.Arg1282Leu	missense	Exon 25 of 26	NP_001374953.1
	TRIM66	NM_001388023.1		c.3818G>T	p.Arg1273Leu	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.3929G>T	p.Arg1310Leu	missense	Exon 24 of 25	ENSP00000495413.1	A0A8Z5E822
	TRIM66	ENST00000705689.1		c.3818G>T	p.Arg1273Leu	missense	Exon 24 of 25	ENSP00000516162.1	A0A994J572
	TRIM66	ENST00000705690.1		c.3494G>T	p.Arg1165Leu	missense	Exon 19 of 20	ENSP00000516163.1	A0A994J7V7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000929 AC: 13 AN: 1399268 Hom.: 0 Cov.: 31 AF XY: 0.00000725 AC XY: 5 AN XY: 690124

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49152

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

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1078966

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 31

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	Uncertain	0.48
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.21
Sift	Benign	0.069	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.61	P
Vest4		0.53
MutPred		0.54		Loss of disorder (P = 0.1482)
MVP		0.45
ClinPred		0.94	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.57
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1460524698; hg19: chr11-8640487;