Variant 5-150004857-A-G 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.5A>G(p.Asp2Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

HMGXB3
NM_014983.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

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:

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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=0.18582037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGXB3	NM_014983.3 link	c.5A>G	p.Asp2Gly	missense_variant	2/20	ENST00000502717.6	NP_055798.3	Q12766Q562E5
HMGXB3	NM_001366501.2 link	c.5A>G	p.Asp2Gly	missense_variant	2/19		NP_001353430.1
HMGXB3	XM_047416963.1 link	c.5A>G	p.Asp2Gly	missense_variant	2/12		XP_047272919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMGXB3	ENST00000502717.6 link	c.5A>G	p.Asp2Gly	missense_variant	2/20	1	NM_014983.3	ENSP00000421917.1	Q12766
HMGXB3	ENST00000613459.4 link	c.743A>G	p.Asp248Gly	missense_variant	3/21	5		ENSP00000479027.1	A0A8C8PVR7
HMGXB3	ENST00000503427.5 link	c.5A>G	p.Asp2Gly	missense_variant	2/21	5		ENSP00000422231.1	E9PEK0

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

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

Dec 09, 2023

The c.5A>G (p.D2G) alteration is located in exon 2 (coding exon 1) of the HMGXB3 gene. This alteration results from a A to G substitution at nucleotide position 5, causing the aspartic acid (D) at amino acid position 2 to be replaced by a glycine (G). 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

0.18

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0069

T;T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.81

L;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.2

.;N;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

.;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.94

P;.;.

Vest4

0.49

MutPred

0.29

Gain of catalytic residue at D248 (P = 0.047);.;.;

MVP

0.12

ClinPred

0.86

GERP RS

5.5

Varity_R

0.24

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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