10-96952154-C-T

Variant names:

• chr10-96952154-C-T
• rs1847691645
• NM_001346516.2:c.290C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346516.2(LCOR):​c.290C>T​(p.Ser97Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. S97Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCOR NM_001346516.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30815846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346516.2. 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.290C>T	p.Ser97Phe	missense	Exon 7 of 8	NP_001333445.1	Q96JN0-3
	LCOR	NM_001170765.2		c.290C>T	p.Ser97Phe	missense	Exon 7 of 8	NP_001164236.1	Q96JN0-1
	LCOR	NM_032440.4		c.290C>T	p.Ser97Phe	missense	Exon 7 of 8	NP_115816.2	Q96JN0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCOR	ENST00000421806.4	TSL:3 MANE Select	c.290C>T	p.Ser97Phe	missense	Exon 7 of 8	ENSP00000490116.2	Q96JN0-3
	LCOR	ENST00000371097.8	TSL:1	c.290C>T	p.Ser97Phe	missense	Exon 7 of 8	ENSP00000360138.3	Q96JN0-1
	LCOR	ENST00000371103.8	TSL:1	c.290C>T	p.Ser97Phe	missense	Exon 7 of 8	ENSP00000360144.3	Q96JN0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.3
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.18	T
Polyphen		0.30	B
Vest4		0.53
MutPred		0.30		Loss of phosphorylation at S97 (P = 0.0108)
MVP		0.17
MPC		0.89
ClinPred		0.96	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.30
Mutation Taster		=89/11	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: rs1847691645; hg19: chr10-98711911;