14-102593022-G-GCCTCGGGCGCCGCCGCCT

Variant names:

• chr14-102593022-G-GCCTCGGGCGCCGCCGCCT
• NM_015156.4:c.141_158dupGGGCGCCGCCGCCTCCTC

Variant summary

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

The NM_015156.4(RCOR1):​c.141_158dupGGGCGCCGCCGCCTCCTC​(p.Ser53_Ala54insGlyAlaAlaAlaSerSer) variant causes a disruptive inframe insertion 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: 33)
• Consequence: RCOR1 NM_015156.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

Genes affected

RCOR1 (HGNC:17441): (REST corepressor 1) This gene encodes a protein that is well-conserved, downregulated at birth, and with a specific role in determining neural cell differentiation. The encoded protein binds to the C-terminal domain of REST (repressor element-1 silencing transcription factor). [provided by RefSeq, Aug 2011]

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 rank	MANE	Protein	UniProt
RCOR1	NM_015156.4	c.141_158dupGGGCGCCGCCGCCTCCTC	p.Ser53_Ala54insGlyAlaAlaAlaSerSer	disruptive_inframe_insertion	Exon 1 of 12	ENST00000262241.7	NP_055971.2
RCOR1	XM_047431148.1	c.141_158dupGGGCGCCGCCGCCTCCTC	p.Ser53_Ala54insGlyAlaAlaAlaSerSer	disruptive_inframe_insertion	Exon 1 of 10		XP_047287104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCOR1	ENST00000262241.7	c.141_158dupGGGCGCCGCCGCCTCCTC	p.Ser53_Ala54insGlyAlaAlaAlaSerSer	disruptive_inframe_insertion	Exon 1 of 12	1	NM_015156.4	ENSP00000262241.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Sep 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.141_158dup, results in the insertion of 6 amino acid(s) of the RCOR1 protein (p.Gly48_Ser53dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RCOR1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr14-103059359;