Variant X-150987866-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005342.4(HMGB3):c.555A>G(p.Glu185Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,194,032 control chromosomes in the GnomAD database, including 119 homozygotes. There are 5,476 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 13 hom., 474 hem., cov: 23)

Exomes 𝑓: 0.015 ( 106 hom. 5002 hem. )

Consequence

HMGB3
NM_005342.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0350

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-150987866-A-G is Benign according to our data. Variant chrX-150987866-A-G is described in ClinVar as [Benign]. Clinvar id is 1964136.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.035 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0151 (1680/111356) while in subpopulation AFR AF= 0.0188 (574/30609). AF 95% confidence interval is 0.0175. There are 13 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB3	NM_005342.4 linkuse as main transcript	c.555A>G	p.Glu185Glu	synonymous_variant	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.555A>G	p.Glu185Glu	synonymous_variant	5/5	1	NM_005342.4	ENSP00000359393.3	O15347
HMGB3	ENST00000448905.6 linkuse as main transcript	c.555A>G	p.Glu185Glu	synonymous_variant	5/5	1		ENSP00000442758.1	O15347
HMGB3	ENST00000455596.5 linkuse as main transcript	c.555A>G	p.Glu185Glu	synonymous_variant	5/5	1		ENSP00000405601.1	E7EQU1
HMGB3	ENST00000419110.5 linkuse as main transcript	c.555A>G	p.Glu185Glu	synonymous_variant	5/5	3		ENSP00000410354.1	E7ES08

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

1680

AN:

111306

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

474

AN XY:

33546

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.0519

Gnomad AMR

AF:

0.00935

Gnomad ASJ

AF:

0.00264

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00115

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0112

AC:

1981

AN:

176617

Hom.:

AF XY:

0.0107

AC XY:

692

AN XY:

64733

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.00637

Gnomad ASJ exome

AF:

0.00215

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0161

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0146

AC:

15836

AN:

1082676

Hom.:

106

Cov.:

AF XY:

0.0142

AC XY:

5002

AN XY:

352860

show subpopulations

Gnomad4 AFR exome

AF:

0.0186

Gnomad4 AMR exome

AF:

0.00623

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00199

Gnomad4 FIN exome

AF:

0.0157

Gnomad4 NFE exome

AF:

0.0167

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.0151

AC:

1680

AN:

111356

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

474

AN XY:

33606

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.00934

Gnomad4 ASJ

AF:

0.00264

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00115

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.0156

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.7

DANN

Benign

0.29

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