Variant 5-150010249-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014983.3(HMGXB3):c.451G>A(p.Val151Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

HMGXB3
NM_014983.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

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]

HMGXB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14709345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGXB3	NM_014983.3 link	c.451G>A	p.Val151Met	missense_variant	4/20	ENST00000502717.6	NP_055798.3	Q12766Q562E5
HMGXB3	XM_047416963.1 link	c.451G>A	p.Val151Met	missense_variant	4/12		XP_047272919.1
HMGXB3	NM_001366501.2 link	c.313-2006G>A		intron_variant			NP_001353430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMGXB3	ENST00000502717.6 link	c.451G>A	p.Val151Met	missense_variant	4/20	1	NM_014983.3	ENSP00000421917.1	Q12766
HMGXB3	ENST00000613459.4 link	c.1189G>A	p.Val397Met	missense_variant	5/21	5		ENSP00000479027.1	A0A8C8PVR7
HMGXB3	ENST00000503427.5 link	c.451G>A	p.Val151Met	missense_variant	4/21	5		ENSP00000422231.1	E9PEK0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1399584

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.451G>A (p.V151M) alteration is located in exon 4 (coding exon 3) of the HMGXB3 gene. This alteration results from a G to A substitution at nucleotide position 451, causing the valine (V) at amino acid position 151 to be replaced by a methionine (M). 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

0.096

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0044

T;T;.

Eigen

Benign

0.068

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.73

.;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0090

.;D;D

Sift4G

Uncertain

0.039

D;D;D

Polyphen

0.70

P;.;.

Vest4

0.35

MutPred

0.28

Loss of sheet (P = 0.0104);.;.;

MVP

0.15

ClinPred

0.47

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over