NM_007078.3:c.609G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_007078.3(LDB3):c.609G>A(p.Ser203Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,611,658 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 61 hom., cov: 34)

Exomes 𝑓: 0.0015 ( 43 hom. )

Consequence

LDB3
NM_007078.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.00900

Publications

1 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:

ENSG00000289258 (HGNC:):

ENSG00000289258 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 10-86681723-G-A is Benign according to our data. Variant chr10-86681723-G-A is described in ClinVar as Benign. ClinVar VariationId is 45550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (2183/152348) while in subpopulation AFR AF = 0.0505 (2102/41584). AF 95% confidence interval is 0.0487. There are 61 homozygotes in GnomAd4. There are 1024 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 61 AD,AR gene

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.609G>A	p.Ser203Ser	synonymous	Exon 5 of 14	NP_009009.1	O75112-1
LDB3	NM_001368067.1	MANE Plus Clinical	c.321+1566G>A		intron	N/A	NP_001354996.1	A0A0S2Z530
LDB3	NM_001171610.2		c.609G>A	p.Ser203Ser	synonymous	Exon 5 of 14	NP_001165081.1	O75112-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDB3	ENST00000361373.9	TSL:1 MANE Select	c.609G>A	p.Ser203Ser	synonymous	Exon 5 of 14	ENSP00000355296.3	O75112-1
ENSG00000289258	ENST00000443292.2	TSL:1	c.2118G>A	p.Ser706Ser	synonymous	Exon 15 of 18	ENSP00000393132.2	C9JWU6
LDB3	ENST00000372056.8	TSL:1	c.609G>A	p.Ser203Ser	synonymous	Exon 4 of 8	ENSP00000361126.4	O75112-4

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2174

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00353

AC:

881

AN:

249662

AF XY:

0.00248

show subpopulations

Gnomad AFR exome

AF:

0.0492

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00152

AC:

2214

AN:

1459310

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

870

AN XY:

725636

show subpopulations

African (AFR)

AF:

0.0520

AC:

1736

AN:

33378

American (AMR)

AF:

0.00202

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.0000697

AC:

AN:

86070

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52996

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000168

AC:

187

AN:

1110644

Other (OTH)

AF:

0.00310

AC:

187

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

132

263

395

526

658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0143

AC:

2183

AN:

152348

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1024

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0505

AC:

2102

AN:

41584

American (AMR)

AF:

0.00333

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68032

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00604

Hom.:

Bravo

AF:

0.0161

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (4)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Myofibrillar myopathy 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.0090

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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