Genetic Variant HMGN5:p.Leu27Ile (chrX-81118482-G-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.79C>A(p.Leu27Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L27F) has been classified as Benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

HMGN5
NM_030763.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

Publications

1 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=0.14150426).

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.79C>A	p.Leu27Ile	missense	Exon 5 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.79C>A	p.Leu27Ile	missense	Exon 5 of 7	ENSP00000350848.2	P82970
HMGN5	ENST00000430960.5	TSL:1	c.79C>A	p.Leu27Ile	missense	Exon 4 of 6	ENSP00000399626.1	Q5JSL0
HMGN5	ENST00000916831.1		c.82C>A	p.Leu28Ile	missense	Exon 4 of 7	ENSP00000586890.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1061540

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

333010

African (AFR)

AF:

0.00

AC:

AN:

25184

American (AMR)

AF:

0.00

AC:

AN:

32279

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18865

East Asian (EAS)

AF:

0.00

AC:

AN:

29663

South Asian (SAS)

AF:

0.00

AC:

AN:

49454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40365

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4049

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

816891

Other (OTH)

AF:

0.00

AC:

AN:

44790

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0077

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.67

M_CAP

Benign

0.0030

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

1.9

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.44

REVEL

Benign

0.033

Sift

Benign

0.34

Sift4G

Benign

0.12

Polyphen

0.26

Vest4

0.13

MutPred

0.34

Gain of catalytic residue at P29 (P = 0.0558)

MVP

0.57

MPC

0.056

ClinPred

0.24

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.0093

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over