Variant 4-164969714-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PP3_Strong

The ENST00000329314.6(TRIM61):c.289T>G(p.Cys97Gly) 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 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM61
ENST00000329314.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Variant links:

Genes affected

TRIM61 (HGNC:24339): (tripartite motif containing 61) 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]

TRIM61 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity TRI61_HUMAN

PP3

MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM61	NM_001414904.1 linkuse as main transcript	c.289T>G	p.Cys97Gly	missense_variant	3/3	ENST00000710271.1	NP_001401833.1
TRIM61	NM_001012414.3 linkuse as main transcript	c.289T>G	p.Cys97Gly	missense_variant	3/5		NP_001012414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRIM61	ENST00000710271.1 linkuse as main transcript	c.289T>G	p.Cys97Gly	missense_variant	3/3		NM_001414904.1	ENSP00000518164	P1
TRIM61	ENST00000329314.6 linkuse as main transcript	c.289T>G	p.Cys97Gly	missense_variant	3/5	1		ENSP00000332288
TRIM61	ENST00000508856.2 linkuse as main transcript	c.289T>G	p.Cys97Gly	missense_variant	3/3			ENSP00000498736	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151226

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000138

AC:

AN:

1451224

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722622

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

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

AF:

0.00

AC:

AN:

151226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73722

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

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

Jul 12, 2023

The c.289T>G (p.C97G) alteration is located in exon 3 (coding exon 1) of the TRIM61 gene. This alteration results from a T to G substitution at nucleotide position 289, causing the cysteine (C) at amino acid position 97 to be replaced by a glycine (G). 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

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.24

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.79

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.95

MetaSVM

Pathogenic

0.92

MutationAssessor

Pathogenic

4.5

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-12

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.74

MutPred

0.69

Loss of stability (P = 0.0107);

MVP

0.58

MPC

4.0

ClinPred

0.89

GERP RS

1.9

Varity_R

0.66

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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