Variant 1-193075828-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001173524.2(RO60):c.589A>G(p.Ile197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,602,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RO60
NM_001173524.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0570

Variant links:

Genes affected

RO60 (HGNC:11313): (Ro60, Y RNA binding protein) Enables RNA binding activity. Involved in cellular response to interferon-alpha and regulation of gene expression. Located in cytosol and nucleoplasm. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

RO60 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021449089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RO60	NM_001173524.2 link	c.589A>G	p.Ile197Val	missense_variant	3/9	ENST00000400968.7	NP_001166995.1	P10155-1A0A024R983

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RO60	ENST00000400968.7 link	c.589A>G	p.Ile197Val	missense_variant	3/9	1	NM_001173524.2	ENSP00000383752.2		P10155-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

239118

Hom.:

AF XY:

0.0000848

AC XY:

AN XY:

129730

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.0000627

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000173

Gnomad SAS exome

AF:

0.0000713

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.000145

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

212

AN:

1450326

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

104

AN XY:

721310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000477

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000144

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000548

AC:

ESP6500EA

AF:

0.000369

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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, 2023

The c.589A>G (p.I197V) alteration is located in exon 3 (coding exon 2) of the TROVE2 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the isoleucine (I) at amino acid position 197 to be replaced by a valine (V). 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

0.053

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.076

T;.;T;.;.;.;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

.;T;.;T;T;T;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.021

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

N;.;N;N;N;N;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.060

N;N;N;N;N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.40

T;D;T;T;T;T;T;T

Sift4G

Benign

0.45

T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;.;.;B;.

Vest4

0.12

MVP

0.14

MPC

0.12

ClinPred

0.018

GERP RS

-0.90

Varity_R

0.013

gMVP

0.079

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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