rs111941389

chr10-86716407-A-Cchr10-86716407-A-Gchr10-86716407-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_Moderate BP6

The NM_007078.3(LDB3):c.1312A>C(p.Thr438Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T438A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LDB3 NM_007078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10600528).
• BP6: Variant 10-86716407-A-C is Benign according to our data. Variant chr10-86716407-A-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDB3	NM_007078.3	c.1312A>C	p.Thr438Pro	missense_variant	10/14	ENST00000361373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDB3	ENST00000361373.9	c.1312A>C	p.Thr438Pro	missense_variant	10/14	1	NM_007078.3	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 446 AN: 22964 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0410

Gnomad ASJ AF: 0.00862

Gnomad EAS AF: 0.00301

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0526

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0411

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000286 AC: 247 AN: 864694 Hom.: 0 Cov.: 34 AF XY: 0.000312 AC XY: 133 AN XY: 425884

Gnomad4 AFR exome AF: 0.000102

Gnomad4 AMR exome AF: 0.000411

Gnomad4 ASJ exome AF: 0.000237

Gnomad4 EAS exome AF: 0.000666

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.000969

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.000391

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0194 AC: 446 AN: 22980 Hom.: 0 Cov.: 0 AF XY: 0.0195 AC XY: 221 AN XY: 11320

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.00862

Gnomad4 EAS AF: 0.00303

Gnomad4 SAS AF: 0.0167

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0404

ExAC AF: 0.0000172 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	13
Dann	Uncertain	0.98
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T;.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.98	N;.;N;N
REVEL	Benign	0.035
Sift	Benign	0.035	D;.;D;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.17, 0.12	.;.;B;B
Vest4		0.21
MVP		0.69
MPC		0.49
ClinPred		0.013	T
GERP RS		3.4
Varity_R		0.18
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs111941389; hg19: chr10-88476164;