Variant X-141176894-T-C 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_012317.4(LDOC1):c.128A>G(p.Gln43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,808 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (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: 1.72

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.123043895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDOC1	NM_012317.4 linkuse as main transcript	c.128A>G	p.Gln43Arg	missense_variant	1/1	ENST00000370526.5	NP_036449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LDOC1	ENST00000370526.5 linkuse as main transcript	c.128A>G	p.Gln43Arg	missense_variant	1/1		NM_012317.4	ENSP00000359557	P1
LDOC1	ENST00000460721.1 linkuse as main transcript	n.123A>G		splice_region_variant, non_coding_transcript_exon_variant	1/2	1
LDOC1	ENST00000670989.1 linkuse as main transcript	n.205A>G		splice_region_variant, non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000553

AC:

AN:

180803

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66071

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00

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

Nov 08, 2022

The c.128A>G (p.Q43R) 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 128, causing the glutamine (Q) at amino acid position 43 to be replaced by an arginine (R). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.74

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.60

M_CAP

Benign

0.023

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

REVEL

Benign

0.030

Sift

Benign

0.094

Sift4G

Benign

0.35

Polyphen

0.24

Vest4

0.14

MutPred

0.14

Gain of MoRF binding (P = 0.0468);

MVP

0.61

MPC

1.5

ClinPred

0.27

GERP RS

3.6

Varity_R

0.22

gMVP

0.90

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