10-86706708-C-T

Position:

chr10-86706708-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007078.3(LDB3):c.1074C>T(p.Ala358Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,611,890 control chromosomes in the GnomAD database, including 1,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 88 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1264 hom. )

Consequence

LDB3
NM_007078.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:14

Conservation

PhyloP100: 0.0710

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:

LDB3 (HGNC:):

LDB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-86706708-C-T is Benign according to our data. Variant chr10-86706708-C-T is described in ClinVar as [Benign]. Clinvar id is 36443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86706708-C-T is described in Lovd as [Likely_benign]. Variant chr10-86706708-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.071 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDB3	NM_007078.3 linkuse as main transcript	c.1074C>T	p.Ala358Ala	synonymous_variant	8/14	ENST00000361373.9	NP_009009.1	O75112-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9 linkuse as main transcript	c.1074C>T	p.Ala358Ala	synonymous_variant	8/14	1	NM_007078.3	ENSP00000355296.3		O75112-1

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4167

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00654

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0510

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0327

AC:

7970

AN:

244014

Hom.:

190

AF XY:

0.0355

AC XY:

4718

AN XY:

132758

show subpopulations

Gnomad AFR exome

AF:

0.00481

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.000439

Gnomad SAS exome

AF:

0.0555

Gnomad FIN exome

AF:

0.0278

Gnomad NFE exome

AF:

0.0443

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0388

AC:

56602

AN:

1459606

Hom.:

1264

Cov.:

AF XY:

0.0397

AC XY:

28843

AN XY:

726062

show subpopulations

Gnomad4 AFR exome

AF:

0.00574

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0582

Gnomad4 FIN exome

AF:

0.0310

Gnomad4 NFE exome

AF:

0.0420

Gnomad4 OTH exome

AF:

0.0330

GnomAD4 genome

AF:

0.0273

AC:

4162

AN:

152284

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2037

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00652

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.0274

Gnomad4 NFE

AF:

0.0427

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0310

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 24, 2008	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 29, 2024	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Dilated cardiomyopathy 1C

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Cytogenetics- Mohapatra Lab, Banaras Hindu University

Aug 21, 2014

- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

curation

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 18, 2011

- -

Myofibrillar myopathy 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.9

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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