dbSNP rs4705403: HMGXB3:c.-252G>A (chr5-150000930-G-A) – 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.-252G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 154,684 control chromosomes in the GnomAD database, including 1,341 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 0.12 ( 1297 hom., cov: 32)

Exomes 𝑓: 0.15 ( 44 hom. )

Consequence

HMGXB3
NM_014983.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.263

Publications

12 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 (MetaRNN=0.0015045702).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HMGXB3	NM_014983.3 link	c.-252G>A	5_prime_UTR_variant	Exon 1 of 20	ENST00000502717.6	NP_055798.3	Q12766Q562E5
HMGXB3	NM_001366501.2 link	c.-252G>A	5_prime_UTR_variant	Exon 1 of 19		NP_001353430.1
HMGXB3	XM_047416963.1 link	c.-252G>A	5_prime_UTR_variant	Exon 1 of 12		XP_047272919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMGXB3	ENST00000502717.6 link	c.-252G>A		5_prime_UTR_variant	Exon 1 of 20	1	NM_014983.3	ENSP00000421917.1	Q12766
HMGXB3	ENST00000613459.4 link	c.487G>A	p.Glu163Lys	missense_variant	Exon 2 of 21	5		ENSP00000479027.1	A0A8C8PVR7
HMGXB3	ENST00000503427.5 link	c.-252G>A		5_prime_UTR_variant	Exon 1 of 21	5		ENSP00000422231.1	E9PEK0

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18033

AN:

151948

Hom.:

1298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0983

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0396

Gnomad FIN

AF:

0.0893

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.151

AC:

396

AN:

2618

Hom.:

Cov.:

AF XY:

0.133

AC XY:

179

AN XY:

1344

show subpopulations

African (AFR)

AF:

0.135

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0426

AC:

AN:

European-Finnish (FIN)

AF:

0.0972

AC:

AN:

422

Middle Eastern (MID)

AF:

0.186

AC:

302

AN:

1620

European-Non Finnish (NFE)

AF:

0.118

AC:

AN:

204

Other (OTH)

AF:

0.0729

AC:

AN:

192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.119

AC:

18035

AN:

152066

Hom.:

1297

Cov.:

AF XY:

0.119

AC XY:

8865

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.0982

AC:

4075

AN:

41502

American (AMR)

AF:

0.260

AC:

3967

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

474

AN:

3470

East Asian (EAS)

AF:

0.101

AC:

521

AN:

5138

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4820

European-Finnish (FIN)

AF:

0.0893

AC:

947

AN:

10604

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7388

AN:

67938

Other (OTH)

AF:

0.139

AC:

293

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

726

1453

2179

2906

3632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.119

Hom.:

2020

Bravo

AF:

0.133

TwinsUK

AF:

0.113

AC:

420

ALSPAC

AF:

0.0976

AC:

376

Asia WGS

AF:

0.0820

AC:

287

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0031

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0015

PhyloP100

0.26

Sift4G

Benign

0.20

Vest4

0.10

MVP

0.32

GERP RS

0.20

PromoterAI

0.062

Neutral

(source)

Varity_R

0.033

Mutation Taster

=299/1

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