Genetic Variant BARX2:p.Lys131Asn (chr11-129436956-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003658.5(BARX2):c.393G>T(p.Lys131Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BARX2
NM_003658.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Variant links:

Genes affected

BARX2 (HGNC:956): (BARX homeobox 2) This gene encodes a member of the homeobox transcription factor family. A highly related protein in mouse has been shown to influence cellular processes that control cell adhesion and remodeling of the actin cytoskeleton in myoblast fusion and chondrogenesis. The encoded protein may also play a role in cancer progression. [provided by RefSeq, Jul 2008]

BARX2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.754

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARX2	NM_003658.5 link	c.393G>T	p.Lys131Asn	missense_variant	Exon 2 of 4	ENST00000281437.6	NP_003649.2	Q9UMQ3
BARX2	XM_011543043.1 link	c.255G>T	p.Lys85Asn	missense_variant	Exon 2 of 4		XP_011541345.1
BARX2	XM_011543044.3 link	c.-43G>T		5_prime_UTR_variant	Exon 2 of 4		XP_011541346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARX2	ENST00000281437.6 link	c.393G>T	p.Lys131Asn	missense_variant	Exon 2 of 4	1	NM_003658.5	ENSP00000281437.4		Q9UMQ3
BARX2	ENST00000605151.1 link	n.783G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459928

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725900

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.393G>T (p.K131N) alteration is located in exon 2 (coding exon 2) of the BARX2 gene. This alteration results from a G to T substitution at nucleotide position 393, causing the lysine (K) at amino acid position 131 to be replaced by an asparagine (N). 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

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.75

MetaSVM

Uncertain

0.60

MutationAssessor

Pathogenic

3.0

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.61

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.65

MutPred

0.38

Loss of methylation at K131 (P = 0.0022);

MVP

0.98

MPC

0.86

ClinPred

0.98

GERP RS

2.6

Varity_R

0.55

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over