Variant ENST00000443292.2:c.1475G>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000443292.2(ENSG00000289258):c.1475G>T(p.Arg492Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 469,870 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ENSG00000289258
ENST00000443292.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.143

Variant links:

Genes affected

ENSG00000289258 (HGNC:):

ENSG00000289258 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030962229).

BP6

Variant 10-86666837-G-T is Benign according to our data. Variant chr10-86666837-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640653.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
LDB3	NM_001368064.1 link	c.-35G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	NP_001354993.1
LDB3	NM_001368063.1 link	c.-35G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	NP_001354992.1
LDB3	NM_001368068.1 link	c.-35G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	NP_001354997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289258	ENST00000443292.2 link	c.1475G>T	p.Arg492Leu	missense_variant	Exon 11 of 18	1		ENSP00000393132.2		C9JWU6

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

273

AN:

151252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000397

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:

0.00

Gnomad OTH

AF:

0.000963

GnomAD3 exomes

AF:

0.000305

AC:

AN:

147742

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

79616

show subpopulations

Gnomad AFR exome

AF:

0.00586

Gnomad AMR exome

AF:

0.0000816

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:

0.0000365

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.000166

AC:

AN:

318496

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

179986

show subpopulations

Gnomad4 AFR exome

AF:

0.00487

Gnomad4 AMR exome

AF:

0.0000733

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000335

Gnomad4 FIN exome

AF:

0.0000373

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000140

GnomAD4 genome

AF:

0.00180

AC:

273

AN:

151374

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

132

AN XY:

73924

show subpopulations

Gnomad4 AFR

AF:

0.00642

Gnomad4 AMR

AF:

0.000397

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000952

Alfa

AF:

0.000820

Hom.:

Bravo

AF:

0.00233

ExAC

AF:

0.000284

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LDB3: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.60

REVEL

Benign

0.071

Sift

Benign

0.19

Sift4G

Benign

0.17

Polyphen

0.0

MVP

0.19

ClinPred

0.0080

GERP RS

1.6

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over