rs111941389

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007078.3(LDB3):c.1312A>C(p.Thr438Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T438A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.019 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LDB3
NM_007078.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

myofibrillar myopathy 4
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
familial dilated cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

LDB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10600528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3 link	c.1312A>C	p.Thr438Pro	missense_variant	Exon 10 of 14	ENST00000361373.9	NP_009009.1	O75112-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9 link	c.1312A>C	p.Thr438Pro	missense_variant	Exon 10 of 14	1	NM_007078.3	ENSP00000355296.3		O75112-1

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

446

AN:

22964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0410

Gnomad ASJ

AF:

0.00862

Gnomad EAS

AF:

0.00301

Gnomad SAS

AF:

0.0167

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.0526

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.00110

AC:

140

AN:

127082

AF XY:

0.00102

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.000830

Gnomad EAS exome

AF:

0.000957

Gnomad FIN exome

AF:

0.000206

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000649

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000286

AC:

247

AN:

864694

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

133

AN XY:

425884

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000102

AC:

AN:

19610

American (AMR)

AF:

0.000411

AC:

AN:

24328

Ashkenazi Jewish (ASJ)

AF:

0.000237

AC:

AN:

12660

East Asian (EAS)

AF:

0.000666

AC:

AN:

10512

South Asian (SAS)

AF:

0.00108

AC:

AN:

49250

European-Finnish (FIN)

AF:

0.000969

AC:

AN:

21678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2086

European-Non Finnish (NFE)

AF:

0.000200

AC:

139

AN:

693862

Other (OTH)

AF:

0.000391

AC:

AN:

30708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.238

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0194

AC:

446

AN:

22980

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

221

AN XY:

11320

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0263

AC:

159

AN:

6040

American (AMR)

AF:

0.0409

AC:

AN:

2174

Ashkenazi Jewish (ASJ)

AF:

0.00862

AC:

AN:

580

East Asian (EAS)

AF:

0.00303

AC:

AN:

660

South Asian (SAS)

AF:

0.0167

AC:

AN:

480

European-Finnish (FIN)

AF:

0.0240

AC:

AN:

1252

Middle Eastern (MID)

AF:

0.0556

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0123

AC:

138

AN:

11252

Other (OTH)

AF:

0.0404

AC:

AN:

322

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.279

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ExAC

AF:

0.0000172

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

.;.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.81

T;.;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;.;M;.

PhyloP100

1.9

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.98

N;.;N;N

REVEL

Benign

0.035

Sift

Benign

0.035

D;.;D;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.17, 0.12

.;.;B;B

Vest4

0.21

MVP

0.69

MPC

0.49

ClinPred

0.013

GERP RS

3.4

Varity_R

0.18

gMVP

0.26

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over