Variant 4-164969989-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001012414.3(TRIM61):c.14C>T(p.Thr5Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,700 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00094 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

TRIM61
NM_001012414.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.373

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010327876).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM61	NM_001012414.3 linkuse as main transcript	c.14C>T	p.Thr5Met	missense_variant	3/5	ENST00000329314.6	NP_001012414.1	Q5EBN2
TRIM61	NM_001414904.1 linkuse as main transcript	c.14C>T	p.Thr5Met	missense_variant	3/3		NP_001401833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM61	ENST00000329314.6 linkuse as main transcript	c.14C>T	p.Thr5Met	missense_variant	3/5	1	NM_001012414.3	ENSP00000332288.5	Q5EBN2
TRIM61	ENST00000710271.1 linkuse as main transcript	c.14C>T	p.Thr5Met	missense_variant	3/3			ENSP00000518164.1
TRIM61	ENST00000508856.2 linkuse as main transcript	c.14C>T	p.Thr5Met	missense_variant	3/3	6		ENSP00000498736.1	A0A494C0U7

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000914

AC:

228

AN:

249430

Hom.:

AF XY:

0.00103

AC XY:

140

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00121

AC:

1764

AN:

1461532

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

918

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00188

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000940

AC:

143

AN:

152168

Hom.:

Cov.:

AF XY:

0.000981

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000379

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00125

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00103

AC:

125

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

Aug 17, 2022

The c.14C>T (p.T5M) alteration is located in exon 3 (coding exon 1) of the TRIM61 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the threonine (T) at amino acid position 5 to be replaced by a methionine (M). 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

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.56

M_CAP

Benign

0.0057

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.33

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.0

REVEL

Benign

0.16

Sift

Uncertain

0.017

Sift4G

Uncertain

0.028

Polyphen

0.99

Vest4

0.041

MVP

0.043

MPC

3.0

ClinPred

0.025

GERP RS

1.2

Varity_R

0.020

gMVP

0.25

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