11-89870905-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.946
Variant links:
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]

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ACMG classification

Classification made for transcript

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
TRIM64BNM_001164397.3 linkc.1066G>C p.Val356Leu missense_variant Exon 7 of 7 ENST00000329862.7 NP_001157869.1 A6NI03
TRIM64BXM_011542955.3 linkc.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
TRIM64BENST00000329862.7 linkc.1066G>C p.Val356Leu missense_variant Exon 7 of 7 1 NM_001164397.3 ENSP00000332969.6 A6NI03

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
LINK: link

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; API