Genetic Variant HMGN5:p.Leu27Phe (chrX-81118482-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030763.3(HMGN5):c.79C>T(p.Leu27Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,172,984 control chromosomes in the GnomAD database, including 70 homozygotes. There are 962 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 33 hom., 481 hem., cov: 23)

Exomes 𝑓: 0.0017 ( 37 hom. 481 hem. )

Consequence

HMGN5
NM_030763.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.91

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028364658).

BP6

Variant X-81118482-G-A is Benign according to our data. Variant chrX-81118482-G-A is described in ClinVar as [Benign]. Clinvar id is 714930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGN5	NM_030763.3 link	c.79C>T	p.Leu27Phe	missense_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.79C>T	p.Leu27Phe	missense_variant	Exon 5 of 7	2	NM_030763.3	ENSP00000350848.2		P82970

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

1773

AN:

111410

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

469

AN XY:

33670

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00676

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00467

AC:

785

AN:

168152

Hom.:

AF XY:

0.00271

AC XY:

151

AN XY:

55644

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000256

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000905

Gnomad OTH exome

AF:

0.00320

GnomAD4 exome

AF:

0.00173

AC:

1834

AN:

1061525

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

481

AN XY:

333011

show subpopulations

Gnomad4 AFR exome

AF:

0.0567

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000453

Gnomad4 OTH exome

AF:

0.00534

GnomAD4 genome

AF:

0.0160

AC:

1783

AN:

111459

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

481

AN XY:

33729

show subpopulations

Gnomad4 AFR

AF:

0.0548

Gnomad4 AMR

AF:

0.00676

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.0146

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.0187

ESP6500AA

AF:

0.0584

AC:

224

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00523

AC:

635

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

- -

Jul 13, 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

0.21

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;.;.;T;T

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.71

T;T;T;T;T;T

MetaRNN

Benign

0.0028

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.;.;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.92

N;N;N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.19

T;T;T;T;T;T

Sift4G

Benign

0.064

T;T;T;D;D;D

Polyphen

0.90

P;.;.;.;.;.

Vest4

0.056

MVP

0.70

MPC

0.13

ClinPred

0.010

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.011

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