Variant 4-164969554-G-A 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.449C>T(p.Pro150Leu) 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 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000071 ( 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: -0.346

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=0.053579092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM61	NM_001414904.1 linkuse as main transcript	c.449C>T	p.Pro150Leu	missense_variant	3/3	ENST00000710271.1
TRIM61	NM_001012414.3 linkuse as main transcript	c.449C>T	p.Pro150Leu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TRIM61	ENST00000710271.1 linkuse as main transcript	c.449C>T	p.Pro150Leu	missense_variant	3/3		NM_001414904.1	P1
TRIM61	ENST00000329314.6 linkuse as main transcript	c.449C>T	p.Pro150Leu	missense_variant	3/5	1
TRIM61	ENST00000508856.2 linkuse as main transcript	c.449C>T	p.Pro150Leu	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.0000663

AC:

AN:

150728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000106

AC:

AN:

188330

Hom.:

AF XY:

0.0000995

AC XY:

AN XY:

100452

show subpopulations

Gnomad AFR exome

AF:

0.000286

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:

0.000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000708

AC:

AN:

1370732

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

682148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000974

Gnomad4 AMR exome

AF:

0.0000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000519

Gnomad4 FIN exome

AF:

0.0000386

Gnomad4 NFE exome

AF:

0.0000803

Gnomad4 OTH exome

AF:

0.0000527

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000663

AC:

AN:

150728

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73498

show subpopulations

Gnomad4 AFR

AF:

0.000146

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000214

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

ExAC

AF:

0.0000750

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

Aug 23, 2021

The c.449C>T (p.P150L) 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 449, causing the proline (P) at amino acid position 150 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

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

Cadd

Benign

2.7

Dann

Benign

0.66

DEOGEN2

Benign

0.088

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.40

M_CAP

Benign

0.0068

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.12

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.074

Sift

Benign

0.17

Sift4G

Benign

0.28

Polyphen

0.0080

Vest4

0.062

MVP

0.043

MPC

1.9

ClinPred

0.022

GERP RS

0.82

Varity_R

0.052

gMVP

0.039

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