rs145655904

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007078.3(LDB3):c.1381T>G(p.Tyr461Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,392,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y461S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

LDB3
NM_007078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 1.49

Publications

0 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):

dilated cardiomyopathy
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: ClinGen
myofibrillar myopathy 4
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24981874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDB3	NM_007078.3	MANE Select	c.1381T>G	p.Tyr461Asp	missense	Exon 10 of 14	NP_009009.1	O75112-1
LDB3	NM_001171610.2		c.1396T>G	p.Tyr466Asp	missense	Exon 10 of 14	NP_001165081.1	O75112-7
LDB3	NM_001368066.1		c.1240T>G	p.Tyr414Asp	missense	Exon 11 of 15	NP_001354995.1	A0A8I5KV04

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDB3	ENST00000361373.9	TSL:1 MANE Select	c.1381T>G	p.Tyr461Asp	missense	Exon 10 of 14	ENSP00000355296.3	O75112-1
LDB3	ENST00000945680.1		c.1585T>G	p.Tyr529Asp	missense	Exon 10 of 14	ENSP00000615739.1
LDB3	ENST00000871464.1		c.1522T>G	p.Tyr508Asp	missense	Exon 11 of 15	ENSP00000541523.1

Frequencies

GnomAD3 genomes

AF:

0.0000151

AC:

AN:

132302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000563

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000159

AC:

AN:

1259986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

624784

show subpopulations

African (AFR)

AF:

0.0000727

AC:

AN:

27518

American (AMR)

AF:

0.00

AC:

AN:

38670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18448

East Asian (EAS)

AF:

0.00

AC:

AN:

20798

South Asian (SAS)

AF:

0.00

AC:

AN:

84364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

981104

Other (OTH)

AF:

0.00

AC:

AN:

46950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

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

AF:

0.0000151

AC:

AN:

132302

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

63430

show subpopulations

African (AFR)

AF:

0.0000563

AC:

AN:

35510

American (AMR)

AF:

0.00

AC:

AN:

12594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3286

East Asian (EAS)

AF:

0.00

AC:

AN:

3906

South Asian (SAS)

AF:

0.00

AC:

AN:

3578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62662

Other (OTH)

AF:

0.00

AC:

AN:

1774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cardiovascular phenotype (1)

Myofibrillar myopathy 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.35

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.39

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.064

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

PhyloP100

1.5

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

REVEL

Benign

0.15

Sift

Benign

0.13

Sift4G

Benign

0.20

Polyphen

0.96

Vest4

0.39

MutPred

0.33

Loss of catalytic residue at Y461 (P = 0.0026)

MVP

0.77

MPC

0.37

ClinPred

0.38

GERP RS

4.3

Varity_R

0.19

gMVP

0.50

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over