Variant 14-102592962-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000262241.7(RCOR1):c.76T>G(p.Ser26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,165,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

RCOR1
ENST00000262241.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.498

Variant links:

Genes affected

RCOR1 (HGNC:17441): (REST corepressor 1) This gene encodes a protein that is well-conserved, downregulated at birth, and with a specific role in determining neural cell differentiation. The encoded protein binds to the C-terminal domain of REST (repressor element-1 silencing transcription factor). [provided by RefSeq, Aug 2011]

RCOR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024735302).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCOR1	NM_015156.4 linkuse as main transcript	c.76T>G	p.Ser26Ala	missense_variant	1/12	ENST00000262241.7	NP_055971.2
RCOR1	XM_047431148.1 linkuse as main transcript	c.76T>G	p.Ser26Ala	missense_variant	1/10		XP_047287104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCOR1	ENST00000262241.7 linkuse as main transcript	c.76T>G	p.Ser26Ala	missense_variant	1/12	1	NM_015156.4	ENSP00000262241	P1

Frequencies

GnomAD3 genomes

AF:

0.000129

AC:

AN:

146734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000338

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:

0.0000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000135

AC:

AN:

22264

Hom.:

AF XY:

0.0000722

AC XY:

AN XY:

13858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000853

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000628

AC:

AN:

1019254

Hom.:

Cov.:

AF XY:

0.0000651

AC XY:

AN XY:

491688

show subpopulations

Gnomad4 AFR exome

AF:

0.000202

Gnomad4 AMR exome

AF:

0.000583

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000671

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000582

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000129

AC:

AN:

146734

Hom.:

Cov.:

AF XY:

0.0000979

AC XY:

AN XY:

71508

show subpopulations

Gnomad4 AFR

AF:

0.000271

Gnomad4 AMR

AF:

0.000338

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 01, 2022

Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with RCOR1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 26 of the RCOR1 protein (p.Ser26Ala). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.66

DANN

Benign

0.38

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.16

M_CAP

Benign

0.0075

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.85

REVEL

Benign

0.030

Sift4G

Benign

0.35

Vest4

0.097

MVP

0.13

MPC

0.53

ClinPred

0.013

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.037

gMVP

0.17

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