rs2034059727

Variant names:

• chr11-8620069-T-A
• rs2034059727
• NM_001388022.1:c.3728A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-8620069-T-A
• chr11-8620069-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001388022.1(TRIM66):​c.3728A>T​(p.His1243Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1243R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM66 NM_001388022.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.98
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3728A>T	p.His1243Leu	missense	Exon 22 of 25	NP_001374951.1	A0A8Z5E822
	TRIM66	NM_001388024.1		c.3644A>T	p.His1215Leu	missense	Exon 23 of 26	NP_001374953.1
	TRIM66	NM_001388023.1		c.3617A>T	p.His1206Leu	missense	Exon 22 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.3728A>T	p.His1243Leu	missense	Exon 22 of 25	ENSP00000495413.1	A0A8Z5E822
	TRIM66	ENST00000705689.1		c.3617A>T	p.His1206Leu	missense	Exon 22 of 25	ENSP00000516162.1	A0A994J572
	TRIM66	ENST00000705690.1		c.3293A>T	p.His1098Leu	missense	Exon 17 of 20	ENSP00000516163.1	A0A994J7V7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.30	N
PhyloP100		8.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.50
Sift	Benign	0.072	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.97	D
Vest4		0.55
MutPred		0.51		Loss of loop (P = 0.1242)
MVP		0.53
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.60
Mutation Taster		=33/67	disease causing

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: rs2034059727; hg19: chr11-8641616;