10-86668546-G-T

Variant names:

• chr10-86668546-G-T
• rs2803556
• NM_007078.3:c.-48G>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007078.3(LDB3):​c.-48G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000735 in 734,928 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 0.00021 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: LDB3 NM_007078.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-86668546-G-T is Benign according to our data. Variant chr10-86668546-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 380120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00021 (32/152174) while in subpopulation AFR AF= 0.000748 (31/41452). AF 95% confidence interval is 0.00054. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.-48G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.-48G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	ENST00000263066.11	NP_001354996.1
LDB3	NM_007078.3	c.-48G>T		5_prime_UTR_variant	Exon 1 of 14	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.-48G>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373	c.-48G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066	c.-48G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	1	NM_001368067.1	ENSP00000263066.7
LDB3	ENST00000361373	c.-48G>T		5_prime_UTR_variant	Exon 1 of 14	1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066	c.-48G>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.1487-123G>T		intron_variant	Intron 11 of 17	1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152174 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000748

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000378 AC: 22 AN: 582754 Hom.: 0 Cov.: 6 AF XY: 0.0000317 AC XY: 10 AN XY: 315604

Gnomad4 AFR exome AF: 0.000903

Gnomad4 AMR exome AF: 0.0000546

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000259

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000126

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152174 Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16 AN XY: 74344

Gnomad4 AFR AF: 0.000748

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 06, 2017

GeneDx

Significance: Likely 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2803556; hg19: chr10-88428303;