Genetic Variant HMGXB3:c.1734+53G>T (chr5-150027170-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014983.3(HMGXB3):c.1734+53G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 1,428,946 control chromosomes in the GnomAD database, including 451,240 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 0.80 ( 49273 hom., cov: 33)

Exomes 𝑓: 0.79 ( 401967 hom. )

Consequence

HMGXB3
NM_014983.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.143

Publications

20 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014983.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	NM_014983.3	MANE Select	c.1734+53G>T		intron	N/A	NP_055798.3	Q12766
	HMGXB3	NM_001366501.2		c.1236+53G>T		intron	N/A	NP_001353430.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGXB3	ENST00000502717.6	TSL:1 MANE Select	c.1734+53G>T	intron	N/A	ENSP00000421917.1	Q12766
HMGXB3	ENST00000613459.4	TSL:5	c.2472+53G>T	intron	N/A	ENSP00000479027.1	A0A8C8PVR7
HMGXB3	ENST00000971018.1		c.1821+53G>T	intron	N/A	ENSP00000641077.1

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122229

AN:

152060

Hom.:

49233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.837

Gnomad AMI

AF:

0.775

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.818

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.832

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.780

GnomAD4 exome

AF:

0.792

AC:

1011152

AN:

1276768

Hom.:

401967

AF XY:

0.787

AC XY:

498104

AN XY:

632558

show subpopulations

African (AFR)

AF:

0.839

AC:

24247

AN:

28884

American (AMR)

AF:

0.778

AC:

25366

AN:

32584

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

18906

AN:

23062

East Asian (EAS)

AF:

0.645

AC:

22504

AN:

34878

South Asian (SAS)

AF:

0.647

AC:

47589

AN:

73542

European-Finnish (FIN)

AF:

0.836

AC:

39688

AN:

47488

Middle Eastern (MID)

AF:

0.751

AC:

3060

AN:

4074

European-Non Finnish (NFE)

AF:

0.805

AC:

787510

AN:

978658

Other (OTH)

AF:

0.789

AC:

42282

AN:

53598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9926

19852

29778

39704

49630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18106

36212

54318

72424

90530

<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:

0.804

AC:

122322

AN:

152178

Hom.:

49273

Cov.:

AF XY:

0.801

AC XY:

59583

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.837

AC:

34732

AN:

41500

American (AMR)

AF:

0.783

AC:

11972

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.818

AC:

2838

AN:

3470

East Asian (EAS)

AF:

0.701

AC:

3629

AN:

5180

South Asian (SAS)

AF:

0.645

AC:

3109

AN:

4820

European-Finnish (FIN)

AF:

0.832

AC:

8812

AN:

10596

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.804

AC:

54684

AN:

68000

Other (OTH)

AF:

0.775

AC:

1638

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1252

2505

3757

5010

6262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.799

Hom.:

98986

Bravo

AF:

0.802

Asia WGS

AF:

0.668

AC:

2328

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.6

(source)

DANN

Benign

0.44

PhyloP100

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over