Variant 10-96955618-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032440.4(LCOR):c.998A>G(p.Asp333Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

LCOR
NM_032440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

Variant links:

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]

LCOR links:

LCOR (HGNC:):

LCOR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39122444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCOR	NM_001346516.2 linkuse as main transcript	c.332+3422A>G		intron_variant		ENST00000421806.4	NP_001333445.1	Q96JN0-3
LCOR	NM_001170765.2 linkuse as main transcript	c.998A>G	p.Asp333Gly	missense_variant	8/8		NP_001164236.1	Q96JN0-1
LCOR	NM_032440.4 linkuse as main transcript	c.998A>G	p.Asp333Gly	missense_variant	8/8		NP_115816.2	Q96JN0-1
LCOR	NM_001170766.2 linkuse as main transcript	c.998A>G	p.Asp333Gly	missense_variant	8/9		NP_001164237.1	Q96JN0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCOR	ENST00000421806.4 linkuse as main transcript	c.332+3422A>G		intron_variant		3	NM_001346516.2	ENSP00000490116.2		Q96JN0-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.998A>G (p.D333G) alteration is located in exon 8 (coding exon 3) of the LCOR gene. This alteration results from a A to G substitution at nucleotide position 998, causing the aspartic acid (D) at amino acid position 333 to be replaced by a glycine (G). 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

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

T;.;T;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;.;D

M_CAP

Benign

0.0023

MetaRNN

Benign

0.39

T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.55

N;N;N;N

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.077

T;T;T;T

Sift4G

Uncertain

0.030

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.50

MutPred

0.23

Gain of catalytic residue at D333 (P = 0.0685);Gain of catalytic residue at D333 (P = 0.0685);Gain of catalytic residue at D333 (P = 0.0685);Gain of catalytic residue at D333 (P = 0.0685);

MVP

0.38

MPC

0.95

ClinPred

0.84

GERP RS

5.7

Varity_R

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over