X-81118464-C-T

Variant names:

• chrX-81118464-C-T
• rs2075260182
• NM_030763.3:c.97G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030763.3(HMGN5):​c.97G>A​(p.Glu33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E33Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: HMGN5 NM_030763.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.97G>A	p.Glu33Lys	missense	Exon 5 of 7	NP_110390.1	P82970

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGN5	ENST00000358130.7	TSL:2 MANE Select	c.97G>A	p.Glu33Lys	missense	Exon 5 of 7	ENSP00000350848.2	P82970
	HMGN5	ENST00000430960.5	TSL:1	c.97G>A	p.Glu33Lys	missense	Exon 4 of 6	ENSP00000399626.1	Q5JSL0
	HMGN5	ENST00000916831.1		c.100G>A	p.Glu34Lys	missense	Exon 4 of 7	ENSP00000586890.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.63		Gain of methylation at E33 (P = 0.0037)
MVP		0.58
MPC		0.14
ClinPred		0.93	D
GERP RS		4.6
Varity_R		0.30
gMVP		0.090
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2075260182; hg19: chrX-80373963;