Variant 4-164969597-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001012414.3(TRIM61):c.406G>C(p.Ala136Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000077 ( 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: 2.27

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 Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM61	NM_001414904.1 linkuse as main transcript	c.406G>C	p.Ala136Pro	missense_variant	3/3	ENST00000710271.1
TRIM61	NM_001012414.3 linkuse as main transcript	c.406G>C	p.Ala136Pro	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TRIM61	ENST00000710271.1 linkuse as main transcript	c.406G>C	p.Ala136Pro	missense_variant	3/3		NM_001414904.1	P1
TRIM61	ENST00000329314.6 linkuse as main transcript	c.406G>C	p.Ala136Pro	missense_variant	3/5	1
TRIM61	ENST00000508856.2 linkuse as main transcript	c.406G>C	p.Ala136Pro	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151052

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000854

Gnomad FIN

AF:

0.0000961

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000810

AC:

AN:

160548

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

84924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000423

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000691

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000770

AC:

103

AN:

1338060

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

667352

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000491

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000592

Gnomad4 OTH exome

AF:

0.0000358

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000595

AC:

AN:

151168

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

73794

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000855

Gnomad4 FIN

AF:

0.0000961

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000128

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

Jun 03, 2022

The c.406G>C (p.A136P) alteration is located in exon 3 (coding exon 1) of the TRIM61 gene. This alteration results from a G to C substitution at nucleotide position 406, causing the alanine (A) at amino acid position 136 to be replaced by a proline (P). 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

0.84

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Benign

0.094

Eigen_PC

Benign

-0.054

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.72

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.66

MutPred

0.79

Loss of MoRF binding (P = 0.0491);

MVP

0.67

MPC

4.2

ClinPred

0.58

GERP RS

3.2

Varity_R

0.54

gMVP

0.34

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