Variant 1-193069140-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001173524.2(RO60):c.86A>T(p.Asp29Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D29H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RO60
NM_001173524.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RO60	NM_001173524.2 link	c.86A>T	p.Asp29Val	missense_variant	2/9	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.86A>T	p.Asp29Val	missense_variant	2/9	1	NM_001173524.2	ENSP00000383752.2		P10155-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249552

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

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

Dec 28, 2023

The c.86A>T (p.D29V) alteration is located in exon 2 (coding exon 1) of the TROVE2 gene. This alteration results from a A to T substitution at nucleotide position 86, causing the aspartic acid (D) at amino acid position 29 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

Uncertain

0.47

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

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

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

.;D;D;.;D;D;D;D

M_CAP

Benign

0.053

MetaRNN

Pathogenic

0.94

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.0

M;.;.;M;M;M;M;M

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.4

D;D;D;D;D;D;D;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0040

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.019

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;.;.;.;D

Vest4

0.88

MutPred

0.82

Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);

MVP

0.58

MPC

0.75

ClinPred

0.98

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.69

gMVP

0.85

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