Genetic Variant HMGN5:p.Glu33Glu (chrX-81118462-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_030763.3(HMGN5):c.99G>A(p.Glu33Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00842 in 1,178,491 control chromosomes in the GnomAD database, including 33 homozygotes. There are 3,023 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 1 hom., 185 hem., cov: 23)

Exomes 𝑓: 0.0087 ( 32 hom. 2838 hem. )

Consequence

HMGN5
NM_030763.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

HMGN5 (HGNC:8013): (high mobility group nucleosome binding domain 5) This gene encodes a nuclear protein with similarities to the high mobility group proteins, HMG14 and HMG17, which suggests that this protein may function as a nucleosomal binding and transcriptional activating protein. [provided by RefSeq, Sep 2009]

HMGN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-81118462-C-T is Benign according to our data. Variant chrX-81118462-C-T is described in ClinVar as [Benign]. Clinvar id is 787692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 185 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGN5	NM_030763.3 link	c.99G>A	p.Glu33Glu	synonymous_variant	Exon 5 of 7	ENST00000358130.7	NP_110390.1	P82970

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGN5	ENST00000358130.7 link	c.99G>A	p.Glu33Glu	synonymous_variant	Exon 5 of 7	2	NM_030763.3	ENSP00000350848.2		P82970

Frequencies

GnomAD3 genomes

AF:

0.00620

AC:

689

AN:

111180

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

185

AN XY:

33462

show subpopulations

Gnomad AFR

AF:

0.000915

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00112

Gnomad FIN

AF:

0.00830

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.00918

Gnomad OTH

AF:

0.00874

GnomAD3 exomes

AF:

0.00632

AC:

1068

AN:

168963

Hom.:

AF XY:

0.00647

AC XY:

362

AN XY:

55945

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00322

Gnomad ASJ exome

AF:

0.0132

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.00696

Gnomad NFE exome

AF:

0.00923

Gnomad OTH exome

AF:

0.00710

GnomAD4 exome

AF:

0.00865

AC:

9232

AN:

1067259

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

2838

AN XY:

337875

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.0151

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00283

Gnomad4 FIN exome

AF:

0.00756

Gnomad4 NFE exome

AF:

0.00968

Gnomad4 OTH exome

AF:

0.00843

GnomAD4 genome

AF:

0.00619

AC:

688

AN:

111232

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

185

AN XY:

33524

show subpopulations

Gnomad4 AFR

AF:

0.000913

Gnomad4 AMR

AF:

0.00535

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00112

Gnomad4 FIN

AF:

0.00830

Gnomad4 NFE

AF:

0.00918

Gnomad4 OTH

AF:

0.00863

Alfa

AF:

0.00831

Hom.:

Bravo

AF:

0.00537

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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