11-89871085-G-T

Variant names:

• chr11-89871085-G-T
• rs2082205457
• NM_001164397.3:c.886C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164397.3(TRIM64B):​c.886C>A​(p.Pro296Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TRIM64B NM_001164397.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.432

Genes affected

TRIM64B (HGNC:37147): (tripartite motif containing 64B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071082294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM64B	NM_001164397.3	c.886C>A	p.Pro296Thr	missense_variant	Exon 7 of 7	ENST00000329862.7	NP_001157869.1
TRIM64B	XM_011542955.3	c.460C>A	p.Pro154Thr	missense_variant	Exon 6 of 6		XP_011541257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM64B	ENST00000329862.7	c.886C>A	p.Pro296Thr	missense_variant	Exon 7 of 7	1	NM_001164397.3	ENSP00000332969.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.886C>A (p.P296T) alteration is located in exon 6 (coding exon 6) of the TRIM64B gene. This alteration results from a C to A substitution at nucleotide position 886, causing the proline (P) at amino acid position 296 to be replaced by a threonine (T). 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	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.35
DANN	Benign	0.057
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00075	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.047
Sift	Benign	0.77	T
Sift4G	Benign	0.93	T
Vest4		0.061
MutPred		0.57		Loss of catalytic residue at P296 (P = 0.0233);
MVP		0.030
ClinPred		0.045	T
GERP RS		-3.1
Varity_R		0.023
gMVP		0.021

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

Other links and lift over

dbSNP: rs2082205457; hg19: chr11-89604253;