1-211289185-C-T

Variant names:

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

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>T​(p.Thr243Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. T243N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RCOR3 NM_001136223.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.090183884).

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>T	p.Thr243Ile	missense	Exon 8 of 12	NP_001129695.1	Q9P2K3-3
	RCOR3	NM_001350069.2		c.824C>T	p.Thr275Ile	missense	Exon 9 of 13	NP_001336998.1
	RCOR3	NM_018254.5		c.554C>T	p.Thr185Ile	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>T	p.Thr243Ile	missense	Exon 8 of 12	ENSP00000413929.2	Q9P2K3-3
	RCOR3	ENST00000367005.8	TSL:1	c.554C>T	p.Thr185Ile	missense	Exon 7 of 11	ENSP00000355972.4	Q9P2K3-1
	RCOR3	ENST00000367006.8	TSL:1	c.728C>T	p.Thr243Ile	missense	Exon 8 of 11	ENSP00000355973.4	Q9P2K3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461360 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111532

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.042
Sift	Benign	0.17	T
Sift4G	Benign	0.13	T
Polyphen		0.0060	B
Vest4		0.17
MutPred		0.14		Loss of phosphorylation at T185 (P = 0.0583)
MVP		0.11
MPC		0.89
ClinPred		0.29	T
GERP RS		5.6
PromoterAI		-0.025	Neutral
Varity_R		0.047
gMVP		0.11
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; COSMIC: COSV65366444; COSMIC: COSV65366444;