NM_030763.3:c.79C>T

Variant names:

• chrX-81118482-G-A
• rs73631719
• NM_030763.3:c.79C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030763.3(HMGN5):​c.79C>T​(p.Leu27Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,172,984 control chromosomes in the GnomAD database, including 70 homozygotes. There are 962 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (33 hom., 481 hem., cov: 23)
  • Exomes 𝑓: 0.0017 (37 hom. 481 hem.)
• Consequence: HMGN5 NM_030763.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.91
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028364658).
• BP6: Variant X-81118482-G-A is Benign according to our data. Variant chrX-81118482-G-A is described in ClinVar as Benign. ClinVar VariationId is 714930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

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.79C>T	p.Leu27Phe	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.79C>T	p.Leu27Phe	missense	Exon 5 of 7	ENSP00000350848.2	P82970
	HMGN5	ENST00000430960.5	TSL:1	c.79C>T	p.Leu27Phe	missense	Exon 4 of 6	ENSP00000399626.1	Q5JSL0
	HMGN5	ENST00000916831.1		c.82C>T	p.Leu28Phe	missense	Exon 4 of 7	ENSP00000586890.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 1773 AN: 111410 Hom.: 33 Cov.: 23

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00676

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00467 AC: 785 AN: 168152 AF XY: 0.00271

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000905

Gnomad OTH exome AF: 0.00320

GnomAD4 exome AF: 0.00173 AC: 1834 AN: 1061525 Hom.: 37 Cov.: 24 AF XY: 0.00144 AC XY: 481 AN XY: 333011

African (AFR) AF: 0.0567 AC: 1427 AN: 25167

American (AMR) AF: 0.00297 AC: 96 AN: 32277

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18866

East Asian (EAS) AF: 0.00 AC: 0 AN: 29663

South Asian (SAS) AF: 0.000222 AC: 11 AN: 49454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40365

Middle Eastern (MID) AF: 0.00593 AC: 24 AN: 4049

European-Non Finnish (NFE) AF: 0.0000453 AC: 37 AN: 816895

Other (OTH) AF: 0.00534 AC: 239 AN: 44789

GnomAD4 genome AF: 0.0160 AC: 1783 AN: 111459 Hom.: 33 Cov.: 23 AF XY: 0.0143 AC XY: 481 AN XY: 33729

African (AFR) AF: 0.0548 AC: 1682 AN: 30668

American (AMR) AF: 0.00676 AC: 71 AN: 10509

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2629

East Asian (EAS) AF: 0.00 AC: 0 AN: 3589

South Asian (SAS) AF: 0.00 AC: 0 AN: 2683

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5964

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 53008

Other (OTH) AF: 0.0146 AC: 22 AN: 1510

Alfa AF: 0.00537 Hom.: 222

Bravo AF: 0.0187

ESP6500AA AF: 0.0584 AC: 224

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00523 AC: 635

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	0.21
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.048
Sift	Benign	0.19	T
Sift4G	Benign	0.064	T
Polyphen		0.90	P
Vest4		0.056
MVP		0.70
MPC		0.13
ClinPred		0.010	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.011
Mutation Taster		=99/1	polymorphism (auto)

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: rs73631719; hg19: chrX-80373981;