10-86699239-TTCTCTCTCTCTCTC-TTCTCTCTC

Position:

• chr10-86699239-TTCTCTCTCTCTCTC-TTCTCTCTC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_007078.3(LDB3):​c.896+6692_896+6697delCTCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,542,488 control chromosomes in the GnomAD database, including 15,362 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10825 hom., cov: 0)
  • Exomes 𝑓: 0.23 (4537 hom.)
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.30

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]

ENSG00000289258 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 10-86699239-TTCTCTC-T is Benign according to our data. Variant chr10-86699239-TTCTCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 43883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86699239-TTCTCTC-T is described in Lovd as [Benign]. Variant chr10-86699239-TTCTCTC-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDB3	NM_007078.3	c.896+6692_896+6697delCTCTCT		intron_variant		ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.756-15_756-10delCTCTCT		intron_variant		ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9	c.896+6692_896+6697delCTCTCT		intron_variant		1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.756-15_756-10delCTCTCT		intron_variant		1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.2406-15_2406-10delCTCTCT		intron_variant		1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 51847 AN: 148542 Hom.: 10803 Cov.: 0

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.324

GnomAD3 exomes AF: 0.263 AC: 59326 AN: 225518 Hom.: 225 AF XY: 0.256 AC XY: 31554 AN XY: 123426

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.314

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.439

Gnomad SAS exome AF: 0.247

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.229 AC: 318588 AN: 1393840 Hom.: 4537 AF XY: 0.228 AC XY: 158716 AN XY: 696076

Gnomad4 AFR exome AF: 0.442

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.349 AC: 51907 AN: 148648 Hom.: 10825 Cov.: 0 AF XY: 0.349 AC XY: 25264 AN XY: 72358

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.325

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 29, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 20, 2011	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 18, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Myofibrillar myopathy 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71019410; hg19: chr10-88458996;