rs10521916

Variant names:

• chrX-23877337-G-A
• rs10521916
• NM_024122.5:c.237+1578C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024122.5(APOO):​c.237+1578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0332 in 112,184 control chromosomes in the GnomAD database, including 63 homozygotes. There are 1,075 hemizygotes 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: 𝑓 0.033 (63 hom., 1075 hem., cov: 23)
• Consequence: APOO NM_024122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 0 publications found

Genes affected

APOO (HGNC:28727): (apolipoprotein O) This gene is a member of the apolipoprotein family. Members of this protein family are involved in the transport and metabolism of lipids. The encoded protein associates with HDL, LDL and VLDL lipoproteins and is characterized by chondroitin-sulfate glycosylation. This protein may be involved in preventing lipid accumulation in the myocardium in obese and diabetic patients. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 4, 5, 12 and 16.[provided by RefSeq, Sep 2009]

APOO Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000296151 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024122.5. 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
	APOO	NM_024122.5	MANE Select	c.237+1578C>T		intron	N/A	NP_077027.1	Q9BUR5-1
	APOO	NR_026545.4		n.473+1578C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOO	ENST00000379226.9	TSL:1 MANE Select	c.237+1578C>T		intron	N/A	ENSP00000368528.4	Q9BUR5-1
	APOO	ENST00000490078.2	TSL:1	n.237+1578C>T		intron	N/A	ENSP00000434341.1	G3V1B6
	APOO	ENST00000899502.1		c.237+1578C>T		intron	N/A	ENSP00000569561.1

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 3722 AN: 112131 Hom.: 63 Cov.: 23

Gnomad AFR AF: 0.00718

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00831

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0502

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0422

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0332 AC: 3722 AN: 112184 Hom.: 63 Cov.: 23 AF XY: 0.0313 AC XY: 1075 AN XY: 34394

African (AFR) AF: 0.00716 AC: 222 AN: 30986

American (AMR) AF: 0.0353 AC: 371 AN: 10513

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 87 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3625

South Asian (SAS) AF: 0.00870 AC: 24 AN: 2759

European-Finnish (FIN) AF: 0.0289 AC: 173 AN: 5980

Middle Eastern (MID) AF: 0.0550 AC: 12 AN: 218

European-Non Finnish (NFE) AF: 0.0520 AC: 2768 AN: 53232

Other (OTH) AF: 0.0417 AC: 64 AN: 1535

Alfa AF: 0.0296 Hom.: 492

Bravo AF: 0.0322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		-0.83
Mutation Taster		=100/0	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: rs10521916; hg19: chrX-23895454;