X-81116269-G-T

Variant names:

• chrX-81116269-G-T
• rs148090107
• NM_030763.3:c.202C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_030763.3(HMGN5):​c.202C>A​(p.Gln68Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,194,289 control chromosomes in the GnomAD database, including 1 homozygotes. There are 7 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (1 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.000016 (0 hom. 3 hem.)
• Consequence: HMGN5 NM_030763.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09413439).
• BS2: High Hemizygotes in GnomAd4 at 4 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.202C>A	p.Gln68Lys	missense	Exon 6 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.202C>A	p.Gln68Lys	missense	Exon 6 of 7	ENSP00000350848.2	P82970
	HMGN5	ENST00000430960.5	TSL:1	c.202C>A	p.Gln68Lys	missense	Exon 5 of 6	ENSP00000399626.1	Q5JSL0
	HMGN5	ENST00000916831.1		c.319C>A	p.Gln107Lys	missense	Exon 6 of 7	ENSP00000586890.1

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 20 AN: 112070 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.000616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000943

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000397 AC: 7 AN: 176305 AF XY: 0.0000163

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000128

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.0000157 AC: 17 AN: 1082219 Hom.: 0 Cov.: 24 AF XY: 0.00000860 AC XY: 3 AN XY: 348751

African (AFR) AF: 0.000383 AC: 10 AN: 26089

American (AMR) AF: 0.00 AC: 0 AN: 34885

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19225

East Asian (EAS) AF: 0.00 AC: 0 AN: 30032

South Asian (SAS) AF: 0.00 AC: 0 AN: 53215

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 828750

Other (OTH) AF: 0.000132 AC: 6 AN: 45585

GnomAD4 genome AF: 0.000178 AC: 20 AN: 112070 Hom.: 1 Cov.: 23 AF XY: 0.000117 AC XY: 4 AN XY: 34254

African (AFR) AF: 0.000616 AC: 19 AN: 30841

American (AMR) AF: 0.0000943 AC: 1 AN: 10605

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3588

South Asian (SAS) AF: 0.00 AC: 0 AN: 2735

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6047

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53169

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.000205 Hom.: 1

Bravo AF: 0.000200

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	0.070
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.5
DANN	Benign	0.56
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L
PhyloP100		1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.061
Sift	Benign	0.93	T
Sift4G	Benign	0.57	T
Polyphen		0.19	B
Vest4		0.077
MVP		0.85
MPC		0.083
ClinPred		0.024	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.014
Mutation Taster		=99/1	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: rs148090107; hg19: chrX-80371768;