1-211259685-A-T

Variant names:

• chr1-211259685-A-T
• NM_001136223.3:c.125A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136223.3(RCOR3):​c.125A>T​(p.Tyr42Phe) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: RCOR3 NM_001136223.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.756
• 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]

ENSG00000297328 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054287225).

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.125A>T	p.Tyr42Phe	missense	Exon 1 of 12	NP_001129695.1	Q9P2K3-3
	RCOR3	NM_001350069.2		c.125A>T	p.Tyr42Phe	missense	Exon 1 of 13	NP_001336998.1
	RCOR3	NM_001136225.3		c.125A>T	p.Tyr42Phe	missense	Exon 1 of 11	NP_001129697.1	Q9P2K3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCOR3	ENST00000419091.7	TSL:2 MANE Select	c.125A>T	p.Tyr42Phe	missense	Exon 1 of 12	ENSP00000413929.2	Q9P2K3-3
	RCOR3	ENST00000367006.8	TSL:1	c.125A>T	p.Tyr42Phe	missense	Exon 1 of 11	ENSP00000355973.4	Q9P2K3-2
	RCOR3	ENST00000905998.1		c.125A>T	p.Tyr42Phe	missense	Exon 1 of 13	ENSP00000576057.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

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	0.047
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.84
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.76
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.10
Sift	Benign	0.66	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.082
MutPred		0.28		Loss of phosphorylation at Y42 (P = 0.0069)
MVP		0.22
MPC		0.73
ClinPred		0.025	T
GERP RS		-1.5
PromoterAI		-0.042	Neutral
gMVP		0.14
Mutation Taster		=88/12	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

hg19: chr1-211433027;