1-211278125-T-A

Position:

• chr1-211278125-T-A

Variant summary

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

The NM_001136223.3(RCOR3):​c.525T>A​(p.Asp175Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RCOR3 NM_001136223.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

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]

RCOR3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCOR3	NM_001136223.3	c.525T>A	p.Asp175Glu	missense_variant	6/12	ENST00000419091.7	NP_001129695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCOR3	ENST00000419091.7	c.525T>A	p.Asp175Glu	missense_variant	6/12	2	NM_001136223.3	ENSP00000413929.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1439942 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716500

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2023

The c.525T>A (p.D175E) alteration is located in exon 6 (coding exon 6) of the RCOR3 gene. This alteration results from a T to A substitution at nucleotide position 525, causing the aspartic acid (D) at amino acid position 175 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;.;.;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	.;.;.;.;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.9	D;D;D;D;D
REVEL	Benign	0.23
Sift	Benign	0.094	T;D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D
Polyphen		0.97, 0.98, 1.0, 0.99	.;D;D;D;D
Vest4		0.57, 0.58, 0.57, 0.56
MutPred		0.56		Gain of methylation at K118 (P = 0.1018);.;.;.;Gain of methylation at K118 (P = 0.1018);
MVP		0.28
MPC		1.8
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.45
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-211451467;