Variant chrX-141176688-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012317.4(LDOC1):c.334A>G(p.Ser112Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,210,627 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

LDOC1
NM_012317.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Variant links:

Genes affected

LDOC1 (HGNC:6548): (LDOC1 regulator of NFKB signaling) The protein encoded by this gene contains a leucine zipper-like motif and a proline-rich region that shares marked similarity with an SH3-binding domain. The protein localizes to the nucleus and is down-regulated in some cancer cell lines. It is thought to regulate the transcriptional response mediated by the nuclear factor kappa B (NF-kappaB). The gene has been proposed as a tumor suppressor gene whose protein product may have an important role in the development and/or progression of some cancers. [provided by RefSeq, Jul 2008]

LDOC1 links:

Genome browser will be placed here

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=0.37752035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDOC1	NM_012317.4 link	c.334A>G	p.Ser112Gly	missense_variant	1/1	ENST00000370526.5	NP_036449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LDOC1	ENST00000370526.5 link	c.334A>G	p.Ser112Gly	missense_variant	1/1	6	NM_012317.4	ENSP00000359557.2	O95751
LDOC1	ENST00000460721.1 link	n.124+205A>G		intron_variant		1
LDOC1	ENST00000670989.1 link	n.206+205A>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112524

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34682

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098103

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363461

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112524

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34682

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Nov 12, 2024

The c.334A>G (p.S112G) alteration is located in exon 1 (coding exon 1) of the LDOC1 gene. This alteration results from a A to G substitution at nucleotide position 334, causing the serine (S) at amino acid position 112 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

0.75

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.75

M_CAP

Benign

0.023

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.21

Sift

Uncertain

0.017

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.39

MutPred

0.50

Gain of catalytic residue at S112 (P = 0.0246);

MVP

0.47

MPC

2.5

ClinPred

0.99

GERP RS

3.7

Varity_R

0.38

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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