chrX-81115003-C-G

Variant names:

• chrX-81115003-C-G
• rs144502161
• NM_030763.3:c.495G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_030763.3(HMGN5):​c.495G>C​(p.Glu165Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,148,328 control chromosomes in the GnomAD database, including 1 homozygotes. There are 127 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., 55 hem., cov: 22)
  • Exomes 𝑓: 0.00021 (1 hom. 72 hem.)
• Consequence: HMGN5 NM_030763.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047929585).
• BP6: Variant X-81115003-C-G is Benign according to our data. Variant chrX-81115003-C-G is described in ClinVar as Benign. ClinVar VariationId is 734671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 55 gene

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.495G>C	p.Glu165Asp	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.495G>C	p.Glu165Asp	missense	Exon 7 of 7	ENSP00000350848.2	P82970
	HMGN5	ENST00000916831.1		c.612G>C	p.Glu204Asp	missense	Exon 7 of 7	ENSP00000586890.1
	HMGN5	ENST00000966207.1		c.609G>C	p.Glu203Asp	missense	Exon 7 of 7	ENSP00000636266.1

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 211 AN: 108889 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000396

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00855

Gnomad NFE AF: 0.0000191

Gnomad OTH AF: 0.000695

GnomAD2 exomes AF: 0.000450 AC: 46 AN: 102175 AF XY: 0.000311

Gnomad AFR exome AF: 0.00521

Gnomad AMR exome AF: 0.000351

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000513

Gnomad OTH exome AF: 0.000682

GnomAD4 exome AF: 0.000206 AC: 214 AN: 1039386 Hom.: 1 Cov.: 31 AF XY: 0.000215 AC XY: 72 AN XY: 335574

African (AFR) AF: 0.00655 AC: 157 AN: 23966

American (AMR) AF: 0.000466 AC: 12 AN: 25750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18157

East Asian (EAS) AF: 0.00 AC: 0 AN: 26780

South Asian (SAS) AF: 0.0000217 AC: 1 AN: 46111

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37048

Middle Eastern (MID) AF: 0.00250 AC: 7 AN: 2798

European-Non Finnish (NFE) AF: 0.00000981 AC: 8 AN: 815131

Other (OTH) AF: 0.000664 AC: 29 AN: 43645

GnomAD4 genome AF: 0.00194 AC: 211 AN: 108942 Hom.: 0 Cov.: 22 AF XY: 0.00174 AC XY: 55 AN XY: 31570

African (AFR) AF: 0.00676 AC: 203 AN: 30044

American (AMR) AF: 0.000396 AC: 4 AN: 10110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2601

East Asian (EAS) AF: 0.00 AC: 0 AN: 3497

South Asian (SAS) AF: 0.00 AC: 0 AN: 2511

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5587

Middle Eastern (MID) AF: 0.00930 AC: 2 AN: 215

European-Non Finnish (NFE) AF: 0.0000191 AC: 1 AN: 52243

Other (OTH) AF: 0.000686 AC: 1 AN: 1458

Alfa AF: 0.000452 Hom.: 8

Bravo AF: 0.00196

ESP6500AA AF: 0.00507 AC: 16

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000685 AC: 20

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.84
DEOGEN2	Benign	0.0067	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.0090
Sift	Benign	0.17	T
Sift4G	Benign	0.071	T
Polyphen		0.61	P
Vest4		0.078
MutPred		0.16		Loss of ubiquitination at K166 (P = 0.0818)
MVP		0.63
MPC		0.019
ClinPred		0.0066	T
GERP RS		1.7
Varity_R		0.086
gMVP		0.00041
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: rs144502161; hg19: chrX-80370502;