rs374336814

Variant names:

• chr10-86692566-G-A
• rs374336814
• NM_007078.3:c.891G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-86692566-G-A
• chr10-86692566-G-C
• chr10-86692566-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_007078.3(LDB3):​c.891G>A​(p.Arg297Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,614,060 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 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: LDB3 NM_007078.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.646
• Publications: 1 publications found

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]

LDB3 Gene-Disease associations (from GenCC):

• myofibrillar myopathy 4

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• familial dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000289258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 10-86692566-G-A is Benign according to our data. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86692566-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 516314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.646 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000944 (138/1461840) while in subpopulation AMR AF = 0.000134 (6/44724). AF 95% confidence interval is 0.0000984. There are 0 homozygotes in GnomAdExome4. There are 80 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.891G>A	p.Arg297Arg	synonymous_variant	Exon 7 of 14	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.750G>A	p.Arg250Arg	synonymous_variant	Exon 8 of 9	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9	c.891G>A	p.Arg297Arg	synonymous_variant	Exon 7 of 14	1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.750G>A	p.Arg250Arg	synonymous_variant	Exon 8 of 9	1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.2400G>A	p.Arg800Arg	synonymous_variant	Exon 17 of 18	1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251488 AF XY: 0.000110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000944 AC: 138 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.000110 AC XY: 80 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000115 AC: 128 AN: 1111970

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74344

African (AFR) AF: 0.0000724 AC: 3 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000567

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jun 16, 2022

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Myofibrillar myopathy 4 Benign:1

Nov 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Oct 12, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.6
DANN	Benign	0.62
PhyloP100		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs374336814; hg19: chr10-88452323; COSMIC: COSV53951208;