10-86699239-TTCTCTCTCTCTCTC-TTC

Position:

• chr10-86699239-TTCTCTCTCTCTCTC-TTC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The ENST00000361373.9(LDB3):​c.896+6686_896+6697del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,562,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: LDB3 ENST00000361373.9 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 10-86699239-TTCTCTCTCTCTC-T is Benign according to our data. Variant chr10-86699239-TTCTCTCTCTCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041152.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDB3	NM_001368067.1	c.756-21_756-10del		intron_variant		ENST00000263066.11	NP_001354996.1
LDB3	NM_007078.3	c.896+6686_896+6697del		intron_variant		ENST00000361373.9	NP_009009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000263066.11	c.756-21_756-10del		intron_variant		1	NM_001368067.1	ENSP00000263066
LDB3	ENST00000361373.9	c.896+6686_896+6697del		intron_variant		1	NM_007078.3	ENSP00000355296	P4

Frequencies

GnomAD3 genomes AF: 0.0000740 AC: 11 AN: 148744 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000989

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 166 AN: 1414032 Hom.: 0 AF XY: 0.000120 AC XY: 85 AN XY: 705828

Gnomad4 AFR exome AF: 0.0000618

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000514

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.0000385

Gnomad4 NFE exome AF: 0.000143

Gnomad4 OTH exome AF: 0.0000512

GnomAD4 genome AF: 0.0000740 AC: 11 AN: 148744 Hom.: 0 Cov.: 0 AF XY: 0.0000553 AC XY: 4 AN XY: 72356

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000989

Gnomad4 NFE AF: 0.000149

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LDB3-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 11, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;