10-102110571-C-A

Variant names:

• chr10-102110571-C-A
• NM_001113407.3:c.483G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001113407.3(LDB1):​c.483G>T​(p.Gln161His) variant causes a missense change involving the alteration of a non-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 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB1	NM_001113407.3	c.483G>T	p.Gln161His	missense_variant	Exon 6 of 11	ENST00000673968.1	NP_001106878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB1	ENST00000673968.1	c.483G>T	p.Gln161His	missense_variant	Exon 6 of 11		NM_001113407.3	ENSP00000501277.1
LDB1	ENST00000361198.9	c.375G>T	p.Gln125His	missense_variant	Exon 6 of 11	1		ENSP00000354616.5
LDB1	ENST00000425280.2	c.483G>T	p.Gln161His	missense_variant	Exon 6 of 11	5		ENSP00000392466.2
LDB1	ENST00000461873.5	n.299G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.483G>T (p.Q161H) alteration is located in exon 6 (coding exon 6) of the LDB1 gene. This alteration results from a G to T substitution at nucleotide position 483, causing the glutamine (Q) at amino acid position 161 to be replaced by a histidine (H). 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	Benign	0.24
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	.;T
Eigen	Benign	0.041
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0075	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.64	.;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.25	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.99	.;D
Vest4		0.73
MutPred		0.52		.;Gain of disorder (P = 0.1224);
MVP		0.66
MPC		1.7
ClinPred		0.90	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.23
gMVP		0.64

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.

Other links and lift over

hg19: chr10-103870328; COSMIC: COSV100756444; COSMIC: COSV100756444;