Genetic Variant NM_030763.3:c.321T>A (chrX-81115177-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030763.3(HMGN5):c.321T>A(p.Asp107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 1,060,115 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000038 ( 0 hom. 1 hem. )

Consequence

HMGN5
NM_030763.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.319

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09313026).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030763.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGN5	NM_030763.3	MANE Select	c.321T>A	p.Asp107Glu	missense	Exon 7 of 7	NP_110390.1	P82970

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMGN5	ENST00000358130.7	TSL:2 MANE Select	c.321T>A	p.Asp107Glu	missense	Exon 7 of 7	ENSP00000350848.2	P82970
HMGN5	ENST00000430960.5	TSL:1	c.321T>A	p.Asp107Glu	missense	Exon 6 of 6	ENSP00000399626.1	Q5JSL0
HMGN5	ENST00000916831.1		c.438T>A	p.Asp146Glu	missense	Exon 7 of 7	ENSP00000586890.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000377

AC:

AN:

1060115

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

338913

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24745

American (AMR)

AF:

0.00

AC:

AN:

30008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18335

East Asian (EAS)

AF:

0.00

AC:

AN:

29181

South Asian (SAS)

AF:

0.00

AC:

AN:

46841

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37991

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3701

European-Non Finnish (NFE)

AF:

0.00000485

AC:

AN:

824882

Other (OTH)

AF:

0.00

AC:

AN:

44431

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.0

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.38

M_CAP

Benign

0.0026

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

-0.32

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

REVEL

Benign

0.082

Sift

Pathogenic

0.0

Sift4G

Benign

0.65

Polyphen

0.99

Vest4

0.063

MutPred

0.24

Gain of methylation at K111 (P = 0.1464)

MVP

0.44

MPC

0.019

ClinPred

0.12

GERP RS

2.6

Varity_R

0.20

gMVP

0.0025

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over