X-141176730-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_012317.4(LDOC1):​c.292G>T​(p.Gly98Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,097,978 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.000012 ( 0 hom. 1 hem. )

Consequence

LDOC1
NM_012317.4 missense

Scores

5
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LDOC1NM_012317.4 linkc.292G>T p.Gly98Trp missense_variant Exon 1 of 1 ENST00000370526.5 NP_036449.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LDOC1ENST00000370526.5 linkc.292G>T p.Gly98Trp missense_variant Exon 1 of 1 6 NM_012317.4 ENSP00000359557.2 O95751
LDOC1ENST00000460721.1 linkn.124+163G>T intron_variant Intron 1 of 1 1
LDOC1ENST00000670989.1 linkn.206+163G>T intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.00000549
AC:
1
AN:
182213
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67427
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:
0.0000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000118
AC:
13
AN:
1097978
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363334
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
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:
0.0000143
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.292G>T (p.G98W) alteration is located in exon 1 (coding exon 1) of the LDOC1 gene. This alteration results from a G to T substitution at nucleotide position 292, causing the glycine (G) at amino acid position 98 to be replaced by a tryptophan (W). 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
0.99
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.81
T
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.94
D
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-7.5
D
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.77
MutPred
0.76
Gain of catalytic residue at L96 (P = 0.0063);
MVP
0.71
MPC
2.8
ClinPred
1.0
D
GERP RS
3.7
Varity_R
0.82
gMVP
0.99

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.

Other links and lift over

dbSNP: rs782148167; hg19: chrX-140270915; COSMIC: COSV100983225; COSMIC: COSV100983225; API