10-86681818-T-C

Variant names:

• chr10-86681818-T-C
• rs375094467
• NM_007078.3:c.689+15T>C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_007078.3(LDB3):​c.689+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,580,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.196

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-86681818-T-C is Benign according to our data. Variant chr10-86681818-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 45553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.689+15T>C		intron_variant	Intron 5 of 13	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.321+1661T>C		intron_variant	Intron 4 of 8	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9	c.689+15T>C		intron_variant	Intron 5 of 13	1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.321+1661T>C		intron_variant	Intron 4 of 8	1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.2198+15T>C		intron_variant	Intron 15 of 17	1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152080 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000274 AC: 6 AN: 219010 Hom.: 0 AF XY: 0.0000338 AC XY: 4 AN XY: 118350

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000340

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000492

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000378 AC: 54 AN: 1428296 Hom.: 0 Cov.: 32 AF XY: 0.0000396 AC XY: 28 AN XY: 707440

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000506

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000465

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152080 Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3 AN XY: 74288

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 19, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.689+15T>C in Intron 04 of LDB3: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 1/7014 European American chromosomes from a broad populat ion by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS;). -

Myofibrillar myopathy 4 Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs375094467; hg19: chr10-88441575;