NM_001113407.3:c.1000delG

Variant names:

• chr10-102109033-AC-A
• NM_001113407.3:c.1000delG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001113407.3(LDB1):​c.1000delG​(p.Val334TyrfsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LDB1 NM_001113407.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

Genes affected

LDB1 (HGNC:6532): (LIM domain binding 1) Enables LIM domain binding activity; RNA polymerase II-specific DNA-binding transcription factor binding activity; and enzyme binding activity. Involved in negative regulation of transcription, DNA-templated and positive regulation of transcription by RNA polymerase II. Located in chromatin. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.191 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113407.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB1	NM_001113407.3	MANE Select	c.1000delG	p.Val334TyrfsTer4	frameshift	Exon 10 of 11	NP_001106878.1	Q86U70-1
	LDB1	NM_003893.5		c.892delG	p.Val298TyrfsTer4	frameshift	Exon 10 of 11	NP_003884.1	Q86U70-2
	LDB1	NM_001321612.2		c.999+1delG		splice_donor intron	N/A	NP_001308541.1	A0A6E1WJ75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB1	ENST00000673968.1	MANE Select	c.1000delG	p.Val334TyrfsTer4	frameshift	Exon 10 of 11	ENSP00000501277.1	Q86U70-1
	LDB1	ENST00000361198.9	TSL:1	c.892delG	p.Val298TyrfsTer4	frameshift	Exon 10 of 11	ENSP00000354616.5	Q86U70-2
	LDB1	ENST00000425280.2	TSL:5	c.999+1delG		splice_donor intron	N/A	ENSP00000392466.2	A0A6E1WJ75

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8
Mutation Taster		=4/196	disease causing

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

hg19: chr10-103868790;