Variant X-150987884-AGAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_005342.4(HMGB3):c.594_596delGGA(p.Glu198del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000777 in 1,154,220 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 114 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.00083 ( 0 hom. 106 hem. )

Consequence

HMGB3
NM_005342.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.34

Variant links:

Genes affected

HMGB3 (HGNC:5004): (high mobility group box 3) This gene encodes a member of a family of proteins containing one or more high mobility group DNA-binding motifs. The encoded protein plays an important role in maintaining stem cell populations, and may be aberrantly expressed in tumor cells. A mutation in this gene was associated with microphthalmia, syndromic 13. There are numerous pseudogenes of this gene on multiple chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

HMGB3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant X-150987884-AGAG-A is Benign according to our data. Variant chrX-150987884-AGAG-A is described in ClinVar as [Benign]. Clinvar id is 3038100.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB3	NM_005342.4 linkuse as main transcript	c.594_596delGGA	p.Glu198del	disruptive_inframe_deletion	5/5	ENST00000325307.12	NP_005333.2	O15347

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMGB3	ENST00000325307.12 linkuse as main transcript	c.594_596delGGA	p.Glu198del	disruptive_inframe_deletion	5/5	1	NM_005342.4	ENSP00000359393.3	O15347
HMGB3	ENST00000448905.6 linkuse as main transcript	c.594_596delGGA	p.Glu198del	disruptive_inframe_deletion	5/5	1		ENSP00000442758.1	O15347
HMGB3	ENST00000419110.5 linkuse as main transcript	c.8_10delGAG		downstream_gene_variant		3		ENSP00000410354.1	E7ES08

Frequencies

GnomAD3 genomes

AF:

0.000279

AC:

AN:

111037

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

33295

show subpopulations

Gnomad AFR

AF:

0.000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000193

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00154

Gnomad FIN

AF:

0.000331

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.000227

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.000467

AC:

AN:

169187

Hom.:

AF XY:

0.000411

AC XY:

AN XY:

60757

show subpopulations

Gnomad AFR exome

AF:

0.000326

Gnomad AMR exome

AF:

0.000307

Gnomad ASJ exome

AF:

0.000139

Gnomad EAS exome

AF:

0.000683

Gnomad SAS exome

AF:

0.000720

Gnomad FIN exome

AF:

0.00123

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.000710

GnomAD4 exome

AF:

0.000830

AC:

866

AN:

1043137

Hom.:

AF XY:

0.000316

AC XY:

106

AN XY:

335215

show subpopulations

Gnomad4 AFR exome

AF:

0.000946

Gnomad4 AMR exome

AF:

0.000321

Gnomad4 ASJ exome

AF:

0.000374

Gnomad4 EAS exome

AF:

0.000748

Gnomad4 SAS exome

AF:

0.000836

Gnomad4 FIN exome

AF:

0.000503

Gnomad4 NFE exome

AF:

0.000891

Gnomad4 OTH exome

AF:

0.000476

GnomAD4 genome

AF:

0.000279

AC:

AN:

111083

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

33351

show subpopulations

Gnomad4 AFR

AF:

0.000262

Gnomad4 AMR

AF:

0.000193

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000283

Gnomad4 SAS

AF:

0.00155

Gnomad4 FIN

AF:

0.000331

Gnomad4 NFE

AF:

0.000227

Gnomad4 OTH

AF:

0.000660

Bravo

AF:

0.000246

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HMGB3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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