10-96955387-C-T

Variant names:

• chr10-96955387-C-T
• rs1483624403
• ENST00000371097.8:c.767C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032440.4(LCOR):​c.767C>T​(p.Pro256Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCOR NM_032440.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50
• Publications: 0 publications found

Genes affected

LCOR (HGNC:29503): (ligand dependent nuclear receptor corepressor) LCOR is a transcriptional corepressor widely expressed in fetal and adult tissues that is recruited to agonist-bound nuclear receptors through a single LxxLL motif, also referred to as a nuclear receptor (NR) box (Fernandes et al., 2003 [PubMed 12535528]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032440.4. 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
	LCOR	NM_001346516.2	MANE Select	c.332+3191C>T		intron	N/A	NP_001333445.1	Q96JN0-3
	LCOR	NM_001170765.2		c.767C>T	p.Pro256Leu	missense	Exon 8 of 8	NP_001164236.1	Q96JN0-1
	LCOR	NM_032440.4		c.767C>T	p.Pro256Leu	missense	Exon 8 of 8	NP_115816.2	Q96JN0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCOR	ENST00000371097.8	TSL:1	c.767C>T	p.Pro256Leu	missense	Exon 8 of 8	ENSP00000360138.3	Q96JN0-1
	LCOR	ENST00000371103.8	TSL:1	c.767C>T	p.Pro256Leu	missense	Exon 8 of 8	ENSP00000360144.3	Q96JN0-1
	LCOR	ENST00000540664.6	TSL:1	c.767C>T	p.Pro256Leu	missense	Exon 8 of 9	ENSP00000443431.1	Q96JN0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.5
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.46		Gain of sheet (P = 0.0085)
MVP		0.70
MPC		0.90
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.52
Mutation Taster		=64/36	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: rs1483624403; hg19: chr10-98715144;