Variant 7-75404890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_198924.4(TRIM73):c.547C>T(p.Arg183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM73
NM_198924.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

Variant links:

Genes affected

TRIM73 (HGNC:18162): (tripartite motif containing 73) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TRIM73 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3584359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM73	NM_198924.4 linkuse as main transcript	c.547C>T	p.Arg183Cys	missense_variant	4/5	ENST00000323819.8	NP_944606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM73	ENST00000323819.8 linkuse as main transcript	c.547C>T	p.Arg183Cys	missense_variant	4/5	1	NM_198924.4	ENSP00000318615	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

57306

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.0000327

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000218

AC:

AN:

1423292

Hom.:

Cov.:

AF XY:

0.0000213

AC XY:

AN XY:

704922

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000480

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000257

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000175

AC:

AN:

57306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

26624

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000327

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000961

Hom.:

ExAC

AF:

0.00000909

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 02, 2021

The c.547C>T (p.R183C) alteration is located in exon 4 (coding exon 3) of the TRIM73 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a cysteine (C). 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

0.094

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

.;T;.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.067

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;T;T;T;.

M_CAP

Benign

0.063

MetaRNN

Benign

0.36

T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.0

.;N;.;.;N

MutationTaster

Benign

0.84

N;N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.1

D;D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

0.88

.;P;.;.;P

Vest4

0.41

MutPred

0.46

.;Loss of disorder (P = 0.0105);Loss of disorder (P = 0.0105);Loss of disorder (P = 0.0105);Loss of disorder (P = 0.0105);

MVP

0.59

ClinPred

0.96

GERP RS

3.4

Varity_R

0.33

gMVP

0.052

Splicing

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