Variant 4-164969933-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000329314.6(TRIM61):c.70A>G(p.Lys24Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

TRIM61
ENST00000329314.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13212478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM61	NM_001414904.1 linkuse as main transcript	c.70A>G	p.Lys24Glu	missense_variant	3/3	ENST00000710271.1	NP_001401833.1
TRIM61	NM_001012414.3 linkuse as main transcript	c.70A>G	p.Lys24Glu	missense_variant	3/5		NP_001012414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRIM61	ENST00000710271.1 linkuse as main transcript	c.70A>G	p.Lys24Glu	missense_variant	3/3		NM_001414904.1	ENSP00000518164	P1
TRIM61	ENST00000329314.6 linkuse as main transcript	c.70A>G	p.Lys24Glu	missense_variant	3/5	1		ENSP00000332288
TRIM61	ENST00000508856.2 linkuse as main transcript	c.70A>G	p.Lys24Glu	missense_variant	3/3			ENSP00000498736	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152054

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000197

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000227

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.70A>G (p.K24E) alteration is located in exon 3 (coding exon 1) of the TRIM61 gene. This alteration results from a A to G substitution at nucleotide position 70, causing the lysine (K) at amino acid position 24 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.70

M_CAP

Benign

0.0014

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.82

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.047

Sift

Benign

0.12

Sift4G

Uncertain

0.047

Polyphen

0.65

Vest4

0.077

MVP

0.043

MPC

2.8

ClinPred

0.24

GERP RS

3.2

Varity_R

0.24

gMVP

0.24

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