X-81115177-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030763.3(HMGN5):​c.321T>C​(p.Asp107Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,060,114 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: HMGN5 NM_030763.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.319 with no splicing effect.

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>C	p.Asp107Asp	synonymous	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>C	p.Asp107Asp	synonymous	Exon 7 of 7	ENSP00000350848.2	P82970
	HMGN5	ENST00000430960.5	TSL:1	c.321T>C	p.Asp107Asp	synonymous	Exon 6 of 6	ENSP00000399626.1	Q5JSL0
	HMGN5	ENST00000916831.1		c.438T>C	p.Asp146Asp	synonymous	Exon 7 of 7	ENSP00000586890.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000150 AC: 2 AN: 133537 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000189 AC: 2 AN: 1060114 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 338912

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: 0.0000685 AC: 2 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: 0.00 AC: 0 AN: 824881

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

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.26
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;