Variant 1-211313521-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001136223.3(RCOR3):c.1415C>T(p.Pro472Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

RCOR3
NM_001136223.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.61

Variant links:

Genes affected

RCOR3 (HGNC:25594): (REST corepressor 3) Predicted to enable enzyme binding activity and transcription corepressor activity. Predicted to be involved in histone deacetylation; negative regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RCOR3 links:

RCOR3 (HGNC:):

RCOR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38290092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCOR3	NM_001136223.3 linkuse as main transcript	c.1415C>T	p.Pro472Leu	missense_variant	12/12	ENST00000419091.7	NP_001129695.1	Q9P2K3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCOR3	ENST00000419091.7 linkuse as main transcript	c.1415C>T	p.Pro472Leu	missense_variant	12/12	2	NM_001136223.3	ENSP00000413929.2		Q9P2K3-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251380

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000809

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Nov 24, 2024

The c.1415C>T (p.P472L) alteration is located in exon 12 (coding exon 12) of the RCOR3 gene. This alteration results from a C to T substitution at nucleotide position 1415, causing the proline (P) at amino acid position 472 to be replaced by a leucine (L). 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.59

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.23

Sift

Benign

0.30

T;T;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.56

MutPred

0.24

.;Loss of catalytic residue at P414 (P = 0.0285);.;

MVP

0.21

MPC

1.9

ClinPred

0.94

GERP RS

5.1

Varity_R

0.24

gMVP

0.54

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