chr10-86699239-TTCTCTCTCTC-T

Variant names:

• chr10-86699239-TTCTCTCTCTC-T
• rs71019410
• NM_007078.3:c.896+6688_896+6697delCTCTCTCTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_007078.3(LDB3):​c.896+6688_896+6697delCTCTCTCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,555,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.001 (1411/1406984) while in subpopulation AFR AF= 0.00366 (116/31714). AF 95% confidence interval is 0.00312. There are 0 homozygotes in gnomad4_exome. There are 659 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.896+6688_896+6697delCTCTCTCTCT		intron_variant	Intron 7 of 13	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.756-19_756-10delCTCTCTCTCT		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+6678delTCTCTCTCTC		intron_variant	Intron 7 of 13	1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.756-38_756-29delTCTCTCTCTC		intron_variant	Intron 8 of 8	1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.2406-38_2406-29delTCTCTCTCTC		intron_variant	Intron 17 of 17	1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 47 AN: 148720 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000991

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00297

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000119

Gnomad OTH AF: 0.000493

GnomAD3 exomes AF: 0.000656 AC: 148 AN: 225518 Hom.: 0 AF XY: 0.000575 AC XY: 71 AN XY: 123426

Gnomad AFR exome AF: 0.000592

Gnomad AMR exome AF: 0.000962

Gnomad ASJ exome AF: 0.000428

Gnomad EAS exome AF: 0.00245

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00189

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000179

GnomAD4 exome AF: 0.00100 AC: 1411 AN: 1406984 Hom.: 0 AF XY: 0.000938 AC XY: 659 AN XY: 702384

Gnomad4 AFR exome AF: 0.00366

Gnomad4 AMR exome AF: 0.000612

Gnomad4 ASJ exome AF: 0.000941

Gnomad4 EAS exome AF: 0.00299

Gnomad4 SAS exome AF: 0.000460

Gnomad4 FIN exome AF: 0.00221

Gnomad4 NFE exome AF: 0.000844

Gnomad4 OTH exome AF: 0.00122

GnomAD4 genome AF: 0.000316 AC: 47 AN: 148826 Hom.: 0 Cov.: 0 AF XY: 0.000524 AC XY: 38 AN XY: 72462

Gnomad4 AFR AF: 0.0000988

Gnomad4 AMR AF: 0.000201

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00297

Gnomad4 NFE AF: 0.000119

Gnomad4 OTH AF: 0.000488

ClinVar

Not reported in ClinVar

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;