Variant 10-86681644-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000361373.9(LDB3):c.530C>A(p.Ala177Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A177V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LDB3
ENST00000361373.9 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.487

Variant links:

Genes affected

LDB3 (HGNC:15710): (LIM domain binding 3) This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]

LDB3 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=0.16545832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDB3	NM_007078.3 linkuse as main transcript	c.530C>A	p.Ala177Asp	missense_variant	5/14	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1 linkuse as main transcript	c.321+1487C>A		intron_variant		ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9 linkuse as main transcript	c.530C>A	p.Ala177Asp	missense_variant	5/14	1	NM_007078.3	ENSP00000355296	P4	O75112-1
LDB3	ENST00000263066.11 linkuse as main transcript	c.321+1487C>A		intron_variant		1	NM_001368067.1	ENSP00000263066		O75112-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726738

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 08, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

.;.;T;T;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.79

T;.;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.17

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;N;N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

N;.;N;N;.;N

REVEL

Benign

0.074

Sift

Uncertain

0.028

D;.;T;T;.;D

Sift4G

Benign

0.087

T;T;T;T;T;T

Polyphen

0.23, 0.55, 0.47

.;.;B;.;P;P

Vest4

0.42

MutPred

0.26

Gain of solvent accessibility (P = 0.0354);Gain of solvent accessibility (P = 0.0354);Gain of solvent accessibility (P = 0.0354);Gain of solvent accessibility (P = 0.0354);Gain of solvent accessibility (P = 0.0354);Gain of solvent accessibility (P = 0.0354);

MVP

0.71

MPC

0.34

ClinPred

0.28

GERP RS

4.9

Varity_R

0.13

gMVP

0.85

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