Variant 4-164969663-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.340C>T(p.Leu114Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000709 in 150,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0013 ( 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: -2.57

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=0.011998057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM61	NM_001012414.3 linkuse as main transcript	c.340C>T	p.Leu114Phe	missense_variant	3/5	ENST00000329314.6	NP_001012414.1	Q5EBN2
TRIM61	NM_001414904.1 linkuse as main transcript	c.340C>T	p.Leu114Phe	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.340C>T	p.Leu114Phe	missense_variant	3/5	1	NM_001012414.3	ENSP00000332288.5	Q5EBN2
TRIM61	ENST00000710271.1 linkuse as main transcript	c.340C>T	p.Leu114Phe	missense_variant	3/3			ENSP00000518164.1
TRIM61	ENST00000508856.2 linkuse as main transcript	c.340C>T	p.Leu114Phe	missense_variant	3/3	6		ENSP00000498736.1	A0A494C0U7

Frequencies

GnomAD3 genomes

AF:

0.000709

AC:

107

AN:

150812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000862

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000966

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00127

AC:

1755

AN:

1383560

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

854

AN XY:

691082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000921

Gnomad4 AMR exome

AF:

0.000506

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.000133

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.000709

AC:

107

AN:

150928

Hom.:

Cov.:

AF XY:

0.000584

AC XY:

AN XY:

73622

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.000861

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000966

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000577

Hom.:

ExAC

AF:

0.000409

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

Apr 24, 2023

The c.340C>T (p.L114F) 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 340, causing the leucine (L) at amino acid position 114 to be replaced by a phenylalanine (F). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.8

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.67

M_CAP

Benign

0.0029

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.034

Sift

Uncertain

0.017

Sift4G

Benign

0.090

Polyphen

0.051

Vest4

0.065

MVP

0.043

MPC

3.1

ClinPred

0.046

GERP RS

0.99

Varity_R

0.16

gMVP

0.054

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