NM_007078.3:c.896+6690_896+6697delCTCTCTCT

Variant names:

• chr10-86699239-TTCTCTCTC-T
• rs71019410
• NM_007078.3:c.896+6690_896+6697delCTCTCTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007078.3(LDB3):​c.896+6690_896+6697delCTCTCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,527,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 0)
  • Exomes 𝑓: 0.023 (0 hom.)
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Benign criteria provided, single submitter 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]

ENSG00000289258 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-86699239-TTCTCTCTC-T is Benign according to our data. Variant chr10-86699239-TTCTCTCTC-T is described in ClinVar as [Benign]. Clinvar id is 1294149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.896+6690_896+6697delCTCTCTCT		intron_variant	Intron 7 of 13	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.756-17_756-10delCTCTCTCT		intron_variant	Intron 8 of 8	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9	c.896+6669_896+6676delTCTCTCTC		intron_variant	Intron 7 of 13	1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.756-38_756-31delTCTCTCTC		intron_variant	Intron 8 of 8	1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.2406-38_2406-31delTCTCTCTC		intron_variant	Intron 17 of 17	1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.000875 AC: 130 AN: 148522 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00121

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000435

Gnomad FIN AF: 0.00119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000179

Gnomad OTH AF: 0.000492

GnomAD3 exomes AF: 0.0450 AC: 10149 AN: 225518 Hom.: 0 AF XY: 0.0415 AC XY: 5122 AN XY: 123426

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0556

Gnomad ASJ exome AF: 0.0281

Gnomad EAS exome AF: 0.171

Gnomad SAS exome AF: 0.0329

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0220

Gnomad OTH exome AF: 0.0294

GnomAD4 exome AF: 0.0227 AC: 31362 AN: 1378786 Hom.: 0 AF XY: 0.0226 AC XY: 15585 AN XY: 688562

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.0209

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.0248

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.000908 AC: 135 AN: 148620 Hom.: 0 Cov.: 0 AF XY: 0.000898 AC XY: 65 AN XY: 72344

Gnomad4 AFR AF: 0.00213

Gnomad4 AMR AF: 0.00121

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.000400

Gnomad4 SAS AF: 0.000654

Gnomad4 FIN AF: 0.00119

Gnomad4 NFE AF: 0.000179

Gnomad4 OTH AF: 0.000487

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;