Variant 4-164969678-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 NM_001012414.3(TRIM61):c.325C>G(p.Gln109Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM61
NM_001012414.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

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_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025644153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM61	NM_001414904.1 linkuse as main transcript	c.325C>G	p.Gln109Glu	missense_variant	3/3	ENST00000710271.1
TRIM61	NM_001012414.3 linkuse as main transcript	c.325C>G	p.Gln109Glu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TRIM61	ENST00000710271.1 linkuse as main transcript	c.325C>G	p.Gln109Glu	missense_variant	3/3		NM_001414904.1	P1
TRIM61	ENST00000329314.6 linkuse as main transcript	c.325C>G	p.Gln109Glu	missense_variant	3/5	1
TRIM61	ENST00000508856.2 linkuse as main transcript	c.325C>G	p.Gln109Glu	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150730

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:

0.000281

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000102

AC:

AN:

176228

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

94258

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:

0.000209

Gnomad OTH exome

AF:

0.000453

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000140

AC:

197

AN:

1406768

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

100

AN XY:

702304

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:

0.000167

Gnomad4 OTH exome

AF:

0.000325

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000126

AC:

AN:

150730

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73418

show subpopulations

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:

0.000281

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000240

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000770

AC:

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

Oct 04, 2022

The c.325C>G (p.Q109E) alteration is located in exon 3 (coding exon 1) of the TRIM61 gene. This alteration results from a C to G substitution at nucleotide position 325, causing the glutamine (Q) at amino acid position 109 to be replaced by a glutamic acid (E). 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

0.068

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.13

DANN

Benign

0.54

DEOGEN2

Benign

0.0028

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.11

M_CAP

Benign

0.0011

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.30

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

1.2

REVEL

Benign

0.066

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.041

Vest4

0.059

MutPred

0.44

Gain of loop (P = 0.069);

MVP

0.068

MPC

2.0

ClinPred

0.029

GERP RS

-5.4

Varity_R

0.062

gMVP

0.080

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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