chr1-211289185-C-A

Variant names:

• chr1-211289185-C-A
• rs1698940120
• NM_001136223.3:c.728C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136223.3(RCOR3):​c.728C>A​(p.Thr243Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: RCOR3 NM_001136223.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

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]

ACMG classification

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=0.098275065).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136223.3. 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
	RCOR3	NM_001136223.3	MANE Select	c.728C>A	p.Thr243Asn	missense	Exon 8 of 12	NP_001129695.1	Q9P2K3-3
	RCOR3	NM_001350069.2		c.824C>A	p.Thr275Asn	missense	Exon 9 of 13	NP_001336998.1
	RCOR3	NM_018254.5		c.554C>A	p.Thr185Asn	missense	Exon 7 of 11	NP_060724.1	Q9P2K3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCOR3	ENST00000419091.7	TSL:2 MANE Select	c.728C>A	p.Thr243Asn	missense	Exon 8 of 12	ENSP00000413929.2	Q9P2K3-3
	RCOR3	ENST00000367005.8	TSL:1	c.554C>A	p.Thr185Asn	missense	Exon 7 of 11	ENSP00000355972.4	Q9P2K3-1
	RCOR3	ENST00000367006.8	TSL:1	c.728C>A	p.Thr243Asn	missense	Exon 8 of 11	ENSP00000355973.4	Q9P2K3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.054	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		3.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.065
Sift	Benign	0.44	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.11		Loss of phosphorylation at T185 (P = 0.0583)
MVP		0.12
MPC		0.91
ClinPred		0.16	T
GERP RS		5.6
PromoterAI		-0.021	Neutral
Varity_R		0.059
gMVP		0.086
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs1698940120; hg19: chr1-211462527;