rs1183434045

Variant names:

• chrX-81115177-A-T
• rs1183434045
• NM_030763.3:c.321T>A

Your query was ambiguous. Multiple possible variants found:

• chrX-81115177-A-T
• chrX-81115177-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.319
• 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 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

Sel.	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.: 24

GnomAD4 exome AF: 0.00000377 AC: 4 AN: 1060115 Hom.: 0 Cov.: 31 AF XY: 0.00000295 AC XY: 1 AN XY: 338913

African (AFR) AF: 0.00 AC: 0 AN: 24745

American (AMR) AF: 0.00 AC: 0 AN: 30008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18335

East Asian (EAS) AF: 0.00 AC: 0 AN: 29181

South Asian (SAS) AF: 0.00 AC: 0 AN: 46841

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37991

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3701

European-Non Finnish (NFE) AF: 0.00000485 AC: 4 AN: 824882

Other (OTH) AF: 0.00 AC: 0 AN: 44431

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.0
DANN	Benign	0.81
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.32
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.082
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.65	T
Polyphen		0.99	D
Vest4		0.063
MutPred		0.24		Gain of methylation at K111 (P = 0.1464)
MVP		0.44
MPC		0.019
ClinPred		0.12	T
GERP RS		2.6
Varity_R		0.20
gMVP		0.0025
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1183434045; hg19: chrX-80370676;