11-89870905-C-G

Variant names:

• chr11-89870905-C-G
• NM_001164397.3:c.1066G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164397.3(TRIM64B):​c.1066G>C​(p.Val356Leu) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TRIM64B NM_001164397.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27843878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM64B	NM_001164397.3	c.1066G>C	p.Val356Leu	missense_variant	Exon 7 of 7	ENST00000329862.7	NP_001157869.1
TRIM64B	XM_011542955.3	c.640G>C	p.Val214Leu	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.1066G>C	p.Val356Leu	missense_variant	Exon 7 of 7	1	NM_001164397.3	ENSP00000332969.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1066G>C (p.V356L) alteration is located in exon 6 (coding exon 6) of the TRIM64B gene. This alteration results from a G to C substitution at nucleotide position 1066, causing the valine (V) at amino acid position 356 to be replaced by a leucine (L). 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	0.33
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Benign	0.21	T
Sift4G	Benign	0.19	T
Vest4		0.41
MutPred		0.70		Gain of catalytic residue at V356 (P = 0.1472);
MVP		0.085
ClinPred		0.17	T
GERP RS		-0.18
Varity_R		0.088
gMVP		0.048

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-89604073;