chr10-102109124-C-A

Variant names:

• chr10-102109124-C-A
• NM_001113407.3:c.910G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001113407.3(LDB1):​c.910G>T​(p.Gly304Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LDB1 NM_001113407.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• 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: Uncertain_significance. The variant received 2 ACMG points.

• 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.910G>T	p.Gly304Cys	missense	Exon 10 of 11	NP_001106878.1	Q86U70-1
	LDB1	NM_001321612.2		c.910G>T	p.Gly304Cys	missense	Exon 10 of 11	NP_001308541.1	A0A6E1WJ75
	LDB1	NM_003893.5		c.802G>T	p.Gly268Cys	missense	Exon 10 of 11	NP_003884.1	Q86U70-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB1	ENST00000673968.1	MANE Select	c.910G>T	p.Gly304Cys	missense	Exon 10 of 11	ENSP00000501277.1	Q86U70-1
	LDB1	ENST00000361198.9	TSL:1	c.802G>T	p.Gly268Cys	missense	Exon 10 of 11	ENSP00000354616.5	Q86U70-2
	LDB1	ENST00000425280.2	TSL:5	c.910G>T	p.Gly304Cys	missense	Exon 10 of 11	ENSP00000392466.2	A0A6E1WJ75

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.45		Loss of glycosylation at S305 (P = 0.0947)
MVP		0.27
MPC		2.0
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.52
gMVP		0.79
Mutation Taster		=30/70	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: chr10-103868881;