Variant 1-211259624-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136223.3(RCOR3):c.64G>A(p.Ala22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,396,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RCOR3
NM_001136223.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.419

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:

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ACMG classification

Classification made for transcript

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=0.073146135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCOR3	NM_001136223.3 linkuse as main transcript	c.64G>A	p.Ala22Thr	missense_variant	1/12	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.64G>A	p.Ala22Thr	missense_variant	1/12	2	NM_001136223.3	ENSP00000413929.2		Q9P2K3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000137

AC:

AN:

146336

Hom.:

AF XY:

0.0000253

AC XY:

AN XY:

79066

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:

0.0000884

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1396162

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

688652

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:

0.000290

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

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

Jul 30, 2023

The c.64G>A (p.A22T) alteration is located in exon 1 (coding exon 1) of the RCOR3 gene. This alteration results from a G to A substitution at nucleotide position 64, causing the alanine (A) at amino acid position 22 to be replaced by a threonine (T). 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

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.97

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.68

T;T;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.073

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.59

N;N;N

REVEL

Benign

0.048

Sift

Benign

0.097

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0010

B;B;P

Vest4

0.062

MutPred

0.17

Gain of glycosylation at A22 (P = 0.0065);Gain of glycosylation at A22 (P = 0.0065);Gain of glycosylation at A22 (P = 0.0065);

MVP

0.26

MPC

0.77

ClinPred

0.35

GERP RS

-0.85

gMVP

0.11

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