chr10-102108204-C-A

Variant names:

• chr10-102108204-C-A
• rs768403370
• NM_001113407.3:c.1125G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113407.3(LDB1):​c.1125G>T​(p.Glu375Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LDB1 NM_001113407.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19489434).

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.1125G>T	p.Glu375Asp	missense	Exon 11 of 11	NP_001106878.1	Q86U70-1
	LDB1	NM_001321612.2		c.1119G>T	p.Glu373Asp	missense	Exon 11 of 11	NP_001308541.1	A0A6E1WJ75
	LDB1	NM_003893.5		c.1017G>T	p.Glu339Asp	missense	Exon 11 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.1125G>T	p.Glu375Asp	missense	Exon 11 of 11	ENSP00000501277.1	Q86U70-1
	LDB1	ENST00000361198.9	TSL:1	c.1017G>T	p.Glu339Asp	missense	Exon 11 of 11	ENSP00000354616.5	Q86U70-2
	LDB1	ENST00000425280.2	TSL:5	c.1119G>T	p.Glu373Asp	missense	Exon 11 of 11	ENSP00000392466.2	A0A6E1WJ75

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.73	N
PhyloP100		2.7
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.40	N
REVEL	Benign	0.16
Sift	Benign	0.65	T
Sift4G	Benign	0.60	T
Polyphen		0.012	B
Vest4		0.32
MutPred		0.49		Loss of stability (P = 0.2326)
MVP		0.56
MPC		0.84
ClinPred		0.54	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.51
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs768403370; hg19: chr10-103867961;