10-96955294-C-T

Variant names:

• chr10-96955294-C-T
• ENST00000371097.8:c.674C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032440.4(LCOR):​c.674C>T​(p.Ala225Val) 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. 12/18 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: 3.50

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09765065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCOR	NM_001346516.2	c.332+3098C>T		intron_variant	Intron 7 of 7	ENST00000421806.4	NP_001333445.1
LCOR	NM_001170765.2	c.674C>T	p.Ala225Val	missense_variant	Exon 8 of 8		NP_001164236.1
LCOR	NM_032440.4	c.674C>T	p.Ala225Val	missense_variant	Exon 8 of 8		NP_115816.2
LCOR	NM_001170766.2	c.674C>T	p.Ala225Val	missense_variant	Exon 8 of 9		NP_001164237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCOR	ENST00000421806.4	c.332+3098C>T		intron_variant	Intron 7 of 7	3	NM_001346516.2	ENSP00000490116.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.674C>T (p.A225V) alteration is located in exon 8 (coding exon 3) of the LCOR gene. This alteration results from a C to T substitution at nucleotide position 674, causing the alanine (A) at amino acid position 225 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T;.;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.91	.;D;.;D
M_CAP	Benign	0.00087	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;N
PROVEAN	Benign	-0.010	N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.038	D;D;D;D
Sift4G	Benign	0.51	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.30
MutPred		0.25		Loss of disorder (P = 0.0524);Loss of disorder (P = 0.0524);Loss of disorder (P = 0.0524);Loss of disorder (P = 0.0524);
MVP		0.24
MPC		0.28
ClinPred		0.34	T
GERP RS		4.4
Varity_R		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-98715051;