Genetic Variant RCOR1:p.Ala3Gly (chr14-102592894-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015156.4(RCOR1):c.8C>G(p.Ala3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000667 in 149,886 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RCOR1
NM_015156.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.995

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13762379).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015156.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCOR1	NM_015156.4	MANE Select	c.8C>G	p.Ala3Gly	missense	Exon 1 of 12	NP_055971.2	Q9UKL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCOR1	ENST00000262241.7	TSL:1 MANE Select	c.8C>G	p.Ala3Gly	missense	Exon 1 of 12	ENSP00000262241.5	Q9UKL0
	RCOR1	ENST00000908570.1		c.8C>G	p.Ala3Gly	missense	Exon 1 of 12	ENSP00000578629.1

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149886

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1082440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

525504

African (AFR)

AF:

0.00

AC:

AN:

21096

American (AMR)

AF:

0.00

AC:

AN:

9922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14596

East Asian (EAS)

AF:

0.00

AC:

AN:

19940

South Asian (SAS)

AF:

0.00

AC:

AN:

35796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2836

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

916250

Other (OTH)

AF:

0.00

AC:

AN:

41220

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149886

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41126

American (AMR)

AF:

0.00

AC:

AN:

15068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67206

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.98

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.48

M_CAP

Benign

0.033

MetaRNN

Benign

0.14

PhyloP100

0.99

PrimateAI

Pathogenic

0.84

Sift4G

Benign

0.54

Vest4

0.15

MVP

0.33

MPC

0.64

GERP RS

1.0

PromoterAI

-0.34

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.074

gMVP

0.55

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over