11-129436966-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003658.5(BARX2):​c.403C>T​(p.Arg135Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,611,182 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

BARX2
NM_003658.5 missense

Scores

16
1
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BARX2NM_003658.5 linkc.403C>T p.Arg135Trp missense_variant Exon 2 of 4 ENST00000281437.6 NP_003649.2 Q9UMQ3
BARX2XM_011543044.3 linkc.-33C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 4 XP_011541346.1
BARX2XM_011543043.1 linkc.265C>T p.Arg89Trp missense_variant Exon 2 of 4 XP_011541345.1
BARX2XM_011543044.3 linkc.-33C>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
BARX2ENST00000281437.6 linkc.403C>T p.Arg135Trp missense_variant Exon 2 of 4 1 NM_003658.5 ENSP00000281437.4 Q9UMQ3
BARX2ENST00000605151.1 linkn.793C>T non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
247974
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
134166
show subpopulations
Gnomad AFR exome
AF:
0.0000623
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1458972
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
725278
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 15, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.403C>T (p.R135W) alteration is located in exon 2 (coding exon 2) of the BARX2 gene. This alteration results from a C to T substitution at nucleotide position 403, causing the arginine (R) at amino acid position 135 to be replaced by a tryptophan (W). 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
0.94
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.47
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.94
D
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.5
M
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-6.6
D
REVEL
Pathogenic
0.75
Sift
Benign
0.24
T
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.89
MVP
0.99
MPC
0.82
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.41
gMVP
0.56

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.

Other links and lift over

dbSNP: rs376412759; hg19: chr11-129306861; API