1-193069322-G-C

Position:

• chr1-193069322-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001173524.2(RO60):​c.268G>C​(p.Glu90Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RO60 NM_001173524.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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]

ACMG classification

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=0.19220158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RO60	NM_001173524.2	c.268G>C	p.Glu90Gln	missense_variant	2/9	ENST00000400968.7	NP_001166995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RO60	ENST00000400968.7	c.268G>C	p.Glu90Gln	missense_variant	2/9	1	NM_001173524.2	ENSP00000383752.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2024

The c.268G>C (p.E90Q) alteration is located in exon 2 (coding exon 1) of the TROVE2 gene. This alteration results from a G to C substitution at nucleotide position 268, causing the glutamic acid (E) at amino acid position 90 to be replaced by a glutamine (Q). 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	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T;.;.;.;T;.
Eigen	Benign	0.098
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;.;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;L;L;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.83	N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.19	T;T;T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T;T;T
Polyphen		0.30	B;B;.;.;.;B;.
Vest4		0.51
MutPred		0.49		Loss of ubiquitination at K88 (P = 0.0618);Loss of ubiquitination at K88 (P = 0.0618);Loss of ubiquitination at K88 (P = 0.0618);Loss of ubiquitination at K88 (P = 0.0618);Loss of ubiquitination at K88 (P = 0.0618);Loss of ubiquitination at K88 (P = 0.0618);.;
MVP		0.36
MPC		0.15
ClinPred		0.69	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.25
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-193038452;