10-86699239-TTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTC

Position:

• chr10-86699239-TTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_007078.3(LDB3):​c.896+6694_896+6697dupCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920

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 -10 ACMG points.

• BP6: Variant 10-86699239-T-TTCTC is Benign according to our data. Variant chr10-86699239-T-TTCTC is described in ClinVar as [Benign]. Clinvar id is 177829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00153 (227/148850) while in subpopulation AMR AF= 0.00508 (76/14962). AF 95% confidence interval is 0.00416. There are 1 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 227 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDB3	NM_007078.3	c.896+6694_896+6697dupCTCT		intron_variant		ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.756-13_756-10dupCTCT		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+6694_896+6697dupCTCT		intron_variant		1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.756-13_756-10dupCTCT		intron_variant		1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.2406-13_2406-10dupCTCT		intron_variant		1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 227 AN: 148742 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00508

Gnomad ASJ AF: 0.000872

Gnomad EAS AF: 0.000996

Gnomad SAS AF: 0.000653

Gnomad FIN AF: 0.00346

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00105 AC: 1478 AN: 1413986 Hom.: 0 Cov.: 0 AF XY: 0.00105 AC XY: 743 AN XY: 705810

Gnomad4 AFR exome AF: 0.000339

Gnomad4 AMR exome AF: 0.00169

Gnomad4 ASJ exome AF: 0.000390

Gnomad4 EAS exome AF: 0.00133

Gnomad4 SAS exome AF: 0.00131

Gnomad4 FIN exome AF: 0.00245

Gnomad4 NFE exome AF: 0.000959

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00153 AC: 227 AN: 148850 Hom.: 1 Cov.: 0 AF XY: 0.00190 AC XY: 138 AN XY: 72470

Gnomad4 AFR AF: 0.000247

Gnomad4 AMR AF: 0.00508

Gnomad4 ASJ AF: 0.000872

Gnomad4 EAS AF: 0.000998

Gnomad4 SAS AF: 0.000653

Gnomad4 FIN AF: 0.00346

Gnomad4 NFE AF: 0.00142

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 22, 2008

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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;