Genetic Variant HMGN5:p.Glu165Asp (chrX-81115003-C-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_030763.3(HMGN5):c.495G>C(p.Glu165Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,148,328 control chromosomes in the GnomAD database, including 1 homozygotes. There are 127 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., 55 hem., cov: 22)

Exomes 𝑓: 0.00021 ( 1 hom. 72 hem. )

Consequence

HMGN5
NM_030763.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.25

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047929585).

BP6

Variant X-81115003-C-G is Benign according to our data. Variant chrX-81115003-C-G is described in ClinVar as [Benign]. Clinvar id is 734671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 55 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGN5	NM_030763.3 link	c.495G>C	p.Glu165Asp	missense_variant	Exon 7 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.495G>C	p.Glu165Asp	missense_variant	Exon 7 of 7	2	NM_030763.3	ENSP00000350848.2		P82970

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

211

AN:

108889

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

AN XY:

31509

show subpopulations

Gnomad AFR

AF:

0.00677

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000396

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00855

Gnomad NFE

AF:

0.0000191

Gnomad OTH

AF:

0.000695

GnomAD3 exomes

AF:

0.000450

AC:

AN:

102175

Hom.:

AF XY:

0.000311

AC XY:

AN XY:

32139

show subpopulations

Gnomad AFR exome

AF:

0.00521

Gnomad AMR exome

AF:

0.000351

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000513

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.000206

AC:

214

AN:

1039386

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

335574

show subpopulations

Gnomad4 AFR exome

AF:

0.00655

Gnomad4 AMR exome

AF:

0.000466

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000217

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000981

Gnomad4 OTH exome

AF:

0.000664

GnomAD4 genome

AF:

0.00194

AC:

211

AN:

108942

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

AN XY:

31570

show subpopulations

Gnomad4 AFR

AF:

0.00676

Gnomad4 AMR

AF:

0.000396

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000191

Gnomad4 OTH

AF:

0.000686

Alfa

AF:

0.000452

Hom.:

Bravo

AF:

0.00196

ESP6500AA

AF:

0.00507

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000685

AC:

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

- -

Apr 04, 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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.84

DEOGEN2

Benign

0.0067

T;T;.

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.36

T;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.82

N;N;N

REVEL

Benign

0.0090

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.071

T;T;T

Polyphen

0.61

P;.;.

Vest4

0.078

MutPred

0.16

Loss of ubiquitination at K166 (P = 0.0818);.;.;

MVP

0.63

MPC

0.019

ClinPred

0.0066

GERP RS

1.7

Varity_R

0.086

gMVP

0.00041

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