Variant 7-75404897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_198924.4(TRIM73):c.554C>T(p.Pro185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,433,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 8)

Exomes 𝑓: 0.00023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM73
NM_198924.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.91

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033019513).

BP6

Variant 7-75404897-C-T is Benign according to our data. Variant chr7-75404897-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2357127.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM73	NM_198924.4 linkuse as main transcript	c.554C>T	p.Pro185Leu	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.554C>T	p.Pro185Leu	missense_variant	4/5	1	NM_198924.4	ENSP00000318615	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

64704

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000117

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000733

AC:

AN:

109140

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

57838

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000230

AC:

330

AN:

1433192

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

169

AN XY:

710304

show subpopulations

Gnomad4 AFR exome

AF:

0.000183

Gnomad4 AMR exome

AF:

0.0000235

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.000335

Gnomad4 SAS exome

AF:

0.000177

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000199

Gnomad4 OTH exome

AF:

0.000204

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000926

AC:

AN:

64788

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

30304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00109

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000117

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.0022

.;T;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.41

T;T;T;T;.

M_CAP

Benign

0.0080

MetaRNN

Benign

0.033

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.81

.;N;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

5.8

N;N;N;N;N

REVEL

Benign

0.099

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;B;.;.;B

Vest4

0.23

MVP

0.27

ClinPred

0.010

GERP RS

0.91

Varity_R

0.033

gMVP

0.021

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