Variant 11-89875659-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PP3

The ENST00000329862.7(TRIM64B):c.359A>C(p.His120Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM64B
ENST00000329862.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

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]

TRIM64B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity TR64B_HUMAN

PP3

MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM64B	NM_001164397.3 linkuse as main transcript	c.359A>C	p.His120Pro	missense_variant	2/7	ENST00000329862.7	NP_001157869.1	A6NI03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM64B	ENST00000329862.7 linkuse as main transcript	c.359A>C	p.His120Pro	missense_variant	2/7	1	NM_001164397.3	ENSP00000332969.6		A6NI03

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000227

AC:

AN:

132102

Hom.:

AF XY:

0.0000141

AC XY:

AN XY:

70922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000574

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000872

AC:

AN:

1376180

Hom.:

Cov.:

AF XY:

0.00000590

AC XY:

AN XY:

678330

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000113

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000265

AC:

AN:

151172

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73838

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.359A>C (p.H120P) alteration is located in exon 1 (coding exon 1) of the TRIM64B gene. This alteration results from a A to C substitution at nucleotide position 359, causing the histidine (H) at amino acid position 120 to be replaced by a proline (P). 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

Uncertain

0.45

BayesDel_addAF

Benign

0.0092

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.29

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.49

M_CAP

Benign

0.0059

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.59

MutationAssessor

Pathogenic

3.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.30

Sift

Benign

0.084

Sift4G

Benign

0.086

Vest4

0.41

MutPred

0.81

Gain of glycosylation at H120 (P = 0.021);

MVP

0.30

ClinPred

0.79

GERP RS

1.0

Varity_R

0.16

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over