ENST00000371097.8:c.956C>G

Variant names:

• chr10-96955576-C-G
• rs889205142
• ENST00000371097.8:c.956C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000371097.8(LCOR):​c.956C>G​(p.Ser319Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S319F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCOR ENST00000371097.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21399939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371097.8. 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+3380C>G		intron	N/A	NP_001333445.1	Q96JN0-3
	LCOR	NM_001170765.2		c.956C>G	p.Ser319Cys	missense	Exon 8 of 8	NP_001164236.1	Q96JN0-1
	LCOR	NM_032440.4		c.956C>G	p.Ser319Cys	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.956C>G	p.Ser319Cys	missense	Exon 8 of 8	ENSP00000360138.3	Q96JN0-1
	LCOR	ENST00000371103.8	TSL:1	c.956C>G	p.Ser319Cys	missense	Exon 8 of 8	ENSP00000360144.3	Q96JN0-1
	LCOR	ENST00000540664.6	TSL:1	c.956C>G	p.Ser319Cys	missense	Exon 8 of 9	ENSP00000443431.1	Q96JN0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251280 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

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	Benign	-0.015	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.7
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.032	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.19		Loss of glycosylation at S319 (P = 0.0021)
MVP		0.20
MPC		0.84
ClinPred		0.39	T
GERP RS		5.7
Varity_R		0.33
Mutation Taster		=98/2	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: rs889205142; hg19: chr10-98715333;