Genetic Variant HMGN5:p.Gly8Val (chrX-81119810-C-A) – 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.23G>T(p.Gly8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,204,023 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,076 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., 51 hem., cov: 23)

Exomes 𝑓: 0.0030 ( 7 hom. 1025 hem. )

Consequence

HMGN5
NM_030763.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0480

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=0.006121278).

BP6

Variant X-81119810-C-A is Benign according to our data. Variant chrX-81119810-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 782073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGN5	NM_030763.3 link	c.23G>T	p.Gly8Val	missense_variant	Exon 3 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.23G>T	p.Gly8Val	missense_variant	Exon 3 of 7	2	NM_030763.3	ENSP00000350848.2		P82970

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

229

AN:

111790

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

AN XY:

33954

show subpopulations

Gnomad AFR

AF:

0.000683

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000475

Gnomad ASJ

AF:

0.00303

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000745

Gnomad FIN

AF:

0.000497

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00354

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.00167

AC:

305

AN:

182649

Hom.:

AF XY:

0.00171

AC XY:

115

AN XY:

67133

show subpopulations

Gnomad AFR exome

AF:

0.000229

Gnomad AMR exome

AF:

0.000476

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000317

Gnomad FIN exome

AF:

0.000438

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.00303

AC:

3306

AN:

1092178

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

1025

AN XY:

357840

show subpopulations

Gnomad4 AFR exome

AF:

0.000342

Gnomad4 AMR exome

AF:

0.000426

Gnomad4 ASJ exome

AF:

0.00217

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000315

Gnomad4 FIN exome

AF:

0.000494

Gnomad4 NFE exome

AF:

0.00364

Gnomad4 OTH exome

AF:

0.00344

GnomAD4 genome

AF:

0.00205

AC:

229

AN:

111845

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

AN XY:

34019

show subpopulations

Gnomad4 AFR

AF:

0.000681

Gnomad4 AMR

AF:

0.000475

Gnomad4 ASJ

AF:

0.00303

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000747

Gnomad4 FIN

AF:

0.000497

Gnomad4 NFE

AF:

0.00354

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.00318

Hom.:

119

Bravo

AF:

0.00184

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00476

AC:

ExAC

AF:

0.00190

AC:

231

EpiCase

AF:

0.00335

EpiControl

AF:

0.00406

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0091

T;.;T;T

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.34

T;T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.0061

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;.;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.051

Sift

Uncertain

0.0030

D;D;T;T

Sift4G

Uncertain

0.021

D;T;T;T

Polyphen

0.11

B;.;.;.

Vest4

0.064

MVP

0.19

MPC

0.073

ClinPred

0.034

GERP RS

-2.1

Varity_R

0.17

gMVP

0.013

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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