rs1035182592

Variant names:

• chr1-211259634-C-A
• rs1035182592
• NM_001136223.3:c.74C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-211259634-C-A
• chr1-211259634-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136223.3(RCOR3):​c.74C>A​(p.Pro25Gln) 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. 12/18 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. P25L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RCOR3 NM_001136223.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13357541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCOR3	NM_001136223.3	c.74C>A	p.Pro25Gln	missense_variant	Exon 1 of 12	ENST00000419091.7	NP_001129695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCOR3	ENST00000419091.7	c.74C>A	p.Pro25Gln	missense_variant	Exon 1 of 12	2	NM_001136223.3	ENSP00000413929.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1394958 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 687978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.94
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.059	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.67	P;P;P
Vest4		0.15
MutPred		0.10		Gain of MoRF binding (P = 0.0477);Gain of MoRF binding (P = 0.0477);Gain of MoRF binding (P = 0.0477);
MVP		0.28
MPC		0.74
ClinPred		0.50	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.26

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

Other links and lift over

dbSNP: rs1035182592; hg19: chr1-211432976;