Genetic Variant HMGXB3:p.Glu900Glu (chr5-150041939-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014983.3(HMGXB3):c.2700A>G(p.Glu900Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,551,208 control chromosomes in the GnomAD database, including 24,784 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 8420 hom., cov: 32)

Exomes 𝑓: 0.13 ( 16364 hom. )

Consequence

HMGXB3
NM_014983.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HMGXB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=0.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGXB3	NM_014983.3 link	c.2700A>G	p.Glu900Glu	synonymous_variant	Exon 15 of 20	ENST00000502717.6	NP_055798.3	Q12766Q562E5
HMGXB3	NM_001366501.2 link	c.2202A>G	p.Glu734Glu	synonymous_variant	Exon 14 of 19		NP_001353430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGXB3	ENST00000502717.6 link	c.2700A>G	p.Glu900Glu	synonymous_variant	Exon 15 of 20	1	NM_014983.3	ENSP00000421917.1		Q12766

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39190

AN:

151974

Hom.:

8394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.579

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0485

Gnomad FIN

AF:

0.0902

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.167

AC:

26091

AN:

156460

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.584

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0973

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.126

AC:

176146

AN:

1399116

Hom.:

16364

Cov.:

AF XY:

0.122

AC XY:

83848

AN XY:

690080

show subpopulations

African (AFR)

AF:

0.595

AC:

18795

AN:

31588

American (AMR)

AF:

0.337

AC:

12018

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4164

AN:

25176

East Asian (EAS)

AF:

0.0909

AC:

3247

AN:

35726

South Asian (SAS)

AF:

0.0514

AC:

4071

AN:

79232

European-Finnish (FIN)

AF:

0.101

AC:

4978

AN:

49270

Middle Eastern (MID)

AF:

0.209

AC:

1191

AN:

5698

European-Non Finnish (NFE)

AF:

0.110

AC:

118596

AN:

1078748

Other (OTH)

AF:

0.157

AC:

9086

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7265

14531

21796

29062

36327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4644

9288

13932

18576

23220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.258

AC:

39260

AN:

152092

Hom.:

8420

Cov.:

AF XY:

0.254

AC XY:

18905

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.579

AC:

24000

AN:

41450

American (AMR)

AF:

0.309

AC:

4717

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

551

AN:

3470

East Asian (EAS)

AF:

0.107

AC:

555

AN:

5174

South Asian (SAS)

AF:

0.0484

AC:

233

AN:

4816

European-Finnish (FIN)

AF:

0.0902

AC:

957

AN:

10612

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7555

AN:

67990

Other (OTH)

AF:

0.241

AC:

506

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1170

2340

3511

4681

5851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.165

Hom.:

6217

Bravo

AF:

0.292

Asia WGS

AF:

0.125

AC:

438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.5

(source)

DANN

Benign

0.60

PhyloP100

0.010

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over