Variant 10-96955527-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032440.4(LCOR):c.907A>G(p.Ser303Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LCOR
NM_032440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11628181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCOR	NM_001346516.2 linkuse as main transcript	c.332+3331A>G		intron_variant		ENST00000421806.4	NP_001333445.1	Q96JN0-3
LCOR	NM_001170765.2 linkuse as main transcript	c.907A>G	p.Ser303Gly	missense_variant	8/8		NP_001164236.1	Q96JN0-1
LCOR	NM_032440.4 linkuse as main transcript	c.907A>G	p.Ser303Gly	missense_variant	8/8		NP_115816.2	Q96JN0-1
LCOR	NM_001170766.2 linkuse as main transcript	c.907A>G	p.Ser303Gly	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+3331A>G		intron_variant		3	NM_001346516.2	ENSP00000490116.2		Q96JN0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251180

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jan 26, 2023

The c.907A>G (p.S303G) 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 907, causing the serine (S) at amino acid position 303 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

Benign

0.059

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;.;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.89

.;D;.;D

M_CAP

Benign

0.0026

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N

PROVEAN

Benign

-0.49

N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.26

MutPred

0.13

Loss of phosphorylation at S303 (P = 0.0082);Loss of phosphorylation at S303 (P = 0.0082);Loss of phosphorylation at S303 (P = 0.0082);Loss of phosphorylation at S303 (P = 0.0082);

MVP

0.58

MPC

0.52

ClinPred

0.36

GERP RS

5.5

Varity_R

0.19

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