Variant chr10-102108314-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001113407.3(LDB1):c.1015G>A(p.Val339Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,682 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

LDB1
NM_001113407.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

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]

LDB1 links:

LDB1 (HGNC:):

LDB1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31642413).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDB1	NM_001113407.3 linkuse as main transcript	c.1015G>A	p.Val339Met	missense_variant	11/11	ENST00000673968.1	NP_001106878.1	Q86U70-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LDB1	ENST00000673968.1 linkuse as main transcript	c.1015G>A	p.Val339Met	missense_variant	11/11		NM_001113407.3	ENSP00000501277.1	Q86U70-1
LDB1	ENST00000361198.9 linkuse as main transcript	c.907G>A	p.Val303Met	missense_variant	11/11	1		ENSP00000354616.5	Q86U70-2
LDB1	ENST00000425280.2 linkuse as main transcript	c.1009G>A	p.Val337Met	missense_variant	11/11	5		ENSP00000392466.2	A0A6E1WJ75

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460682

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.1015G>A (p.V339M) alteration is located in exon 11 (coding exon 11) of the LDB1 gene. This alteration results from a G to A substitution at nucleotide position 1015, causing the valine (V) at amino acid position 339 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

.;D

Eigen

Benign

-0.084

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.089

Sift

Benign

0.083

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0010

.;B

Vest4

0.19

MutPred

0.73

.;Gain of disorder (P = 0.0561);

MVP

0.76

MPC

0.89

ClinPred

0.63

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.93

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over