10-96955330-C-G

Variant names:

• chr10-96955330-C-G
• ENST00000371097.8:c.710C>G

Variant summary

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

The NM_032440.4(LCOR):​c.710C>G​(p.Ala237Gly) 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. 15/19 in silico tools predict a benign 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: 1.04
• 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: 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=0.056140542).

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+3134C>G		intron	N/A	NP_001333445.1	Q96JN0-3
	LCOR	NM_001170765.2		c.710C>G	p.Ala237Gly	missense	Exon 8 of 8	NP_001164236.1	Q96JN0-1
	LCOR	NM_032440.4		c.710C>G	p.Ala237Gly	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.710C>G	p.Ala237Gly	missense	Exon 8 of 8	ENSP00000360138.3	Q96JN0-1
	LCOR	ENST00000371103.8	TSL:1	c.710C>G	p.Ala237Gly	missense	Exon 8 of 8	ENSP00000360144.3	Q96JN0-1
	LCOR	ENST00000540664.6	TSL:1	c.710C>G	p.Ala237Gly	missense	Exon 8 of 9	ENSP00000443431.1	Q96JN0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.0
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.085
Sift	Benign	0.42	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.23		Loss of helix (P = 0.0104)
MVP		0.13
MPC		0.28
ClinPred		0.18	T
GERP RS		5.3
Varity_R		0.12
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr10-98715087;