X-81114704-T-G

Variant names:

• chrX-81114704-T-G
• NM_030763.3:c.794A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030763.3(HMGN5):​c.794A>C​(p.Glu265Ala) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: HMGN5 NM_030763.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07823965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGN5	NM_030763.3	c.794A>C	p.Glu265Ala	missense_variant	Exon 7 of 7	ENST00000358130.7	NP_110390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGN5	ENST00000358130.7	c.794A>C	p.Glu265Ala	missense_variant	Exon 7 of 7	2	NM_030763.3	ENSP00000350848.2
HMGN5	ENST00000447319.5	c.*131A>C		downstream_gene_variant		3		ENSP00000408060.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.794A>C (p.E265A) alteration is located in exon 7 (coding exon 6) of the HMGN5 gene. This alteration results from a A to C substitution at nucleotide position 794, causing the glutamic acid (E) at amino acid position 265 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.079
Sift	Benign	0.12	T
Sift4G	Uncertain	0.018	D
Polyphen		0.16	B
Vest4		0.15
MutPred		0.19		Loss of solvent accessibility (P = 0.0435);
MVP		0.20
MPC		0.020
ClinPred		0.073	T
GERP RS		-0.51
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.3
Varity_R		0.063
gMVP		0.00053

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-80370203;