Variant 11-89968705-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000533122.4(TRIM64):c.202G>C(p.Val68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00020 ( 19 hom. )

Failed GnomAD Quality Control

Consequence

TRIM64
ENST00000533122.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0220

Variant links:

Genes affected

TRIM64 (HGNC:14663): (tripartite motif containing 64) 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]

TRIM64 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048527777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM64	NM_001136486.2 linkuse as main transcript	c.202G>C	p.Val68Leu	missense_variant	2/7	ENST00000533122.4	NP_001129958.1	A6NGJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM64	ENST00000533122.4 linkuse as main transcript	c.202G>C	p.Val68Leu	missense_variant	2/7	1	NM_001136486.2	ENSP00000483764.1		A6NGJ6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

40548

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000629

AC:

AN:

79510

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

41718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000304

Gnomad SAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000204

AC:

152

AN:

745806

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

367550

show subpopulations

Gnomad4 AFR exome

AF:

0.00831

Gnomad4 AMR exome

AF:

0.0000387

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000215

Gnomad4 SAS exome

AF:

0.000453

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000317

Gnomad4 OTH exome

AF:

0.000235

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

40564

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20110

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00253

Hom.:

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

Apr 25, 2022

The c.202G>C (p.V68L) alteration is located in exon 1 (coding exon 1) of the TRIM64 gene. This alteration results from a G to C substitution at nucleotide position 202, causing the valine (V) at amino acid position 68 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

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.020

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.23

MetaRNN

Benign

0.049

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.48

Sift4G

Uncertain

0.014

Polyphen

0.15

Vest4

0.039

MVP

0.048

GERP RS

-2.0

Varity_R

0.027

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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