5-150010271-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014983.3(HMGXB3):​c.473C>T​(p.Pro158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,551,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

HMGXB3
NM_014983.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84
Variant links:
Genes affected
HMGXB3 (HGNC:28982): (HMG-box containing 3) This gene is one of the non-canonical high mobility group (HMG) genes. The encoded protein contains an HMG-box domain found in DNA binding proteins such as transcription factors and chromosomal proteins. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.063590676).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMGXB3NM_014983.3 linkc.473C>T p.Pro158Leu missense_variant Exon 4 of 20 ENST00000502717.6 NP_055798.3 Q12766Q562E5
HMGXB3XM_047416963.1 linkc.473C>T p.Pro158Leu missense_variant Exon 4 of 12 XP_047272919.1
HMGXB3NM_001366501.2 linkc.313-1984C>T intron_variant Intron 3 of 18 NP_001353430.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMGXB3ENST00000502717.6 linkc.473C>T p.Pro158Leu missense_variant Exon 4 of 20 1 NM_014983.3 ENSP00000421917.1 Q12766
HMGXB3ENST00000613459.4 linkc.1211C>T p.Pro404Leu missense_variant Exon 5 of 21 5 ENSP00000479027.1 A0A8C8PVR7
HMGXB3ENST00000503427.5 linkc.473C>T p.Pro158Leu missense_variant Exon 4 of 21 5 ENSP00000422231.1 E9PEK0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000255
AC:
4
AN:
156890
Hom.:
0
AF XY:
0.0000120
AC XY:
1
AN XY:
83078
show subpopulations
Gnomad AFR exome
AF:
0.000125
Gnomad AMR exome
AF:
0.000121
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000114
AC:
16
AN:
1399520
Hom.:
0
Cov.:
31
AF XY:
0.0000101
AC XY:
7
AN XY:
690260
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.000140
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000649
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.0000264

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.473C>T (p.P158L) alteration is located in exon 4 (coding exon 3) of the HMGXB3 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the proline (P) at amino acid position 158 to be replaced by a leucine (L). 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
0.074
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0069
T;T;.
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.028
FATHMM_MKL
Benign
0.31
N
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.064
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.81
L;.;.
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.5
.;N;N
REVEL
Benign
0.12
Sift
Benign
0.087
.;T;T
Sift4G
Benign
0.084
T;T;T
Polyphen
0.0010
B;.;.
Vest4
0.049
MutPred
0.20
Loss of relative solvent accessibility (P = 0.008);.;.;
MVP
0.20
ClinPred
0.042
T
GERP RS
5.9
Varity_R
0.083
gMVP
0.53

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: rs61733398; hg19: chr5-149389834; API