10-101228613-T-G

Position:

• chr10-101228613-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_006562.5(LBX1):​c.203A>C​(p.Gln68Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LBX1 NM_006562.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.94

Genes affected

LBX1 (HGNC:16960): (ladybird homeobox 1) This gene and the orthologous mouse gene were found by their homology to the Drosophila lady bird early and late homeobox genes. In the mouse, this gene is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10137695).
• BP6: Variant 10-101228613-T-G is Benign according to our data. Variant chr10-101228613-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2569371.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LBX1	NM_006562.5	c.203A>C	p.Gln68Pro	missense_variant	1/2	ENST00000370193.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LBX1	ENST00000370193.4	c.203A>C	p.Gln68Pro	missense_variant	1/2	1	NM_006562.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.85
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.17	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	-0.81	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	1.0	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.37		Loss of catalytic residue at Q68 (P = 0.0686);
MVP		0.38
ClinPred		0.46	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.50

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: chr10-102988370; COSMIC: COSV64622034; COSMIC: COSV64622034;