Genetic Variant ASPN:p.Asp49_Asp51del (chr9-92474742-CTCATCATCA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000375544.7(ASPN):c.147_155delTGATGATGA(p.Asp49_Asp51del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00038 in 1,533,548 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

ASPN
ENST00000375544.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52

Publications

9 publications found

Variant links:

Genes affected

ASPN (HGNC:14872): (asporin) This gene encodes a cartilage extracellular protein that is member of the small leucine-rich proteoglycan family. The encoded protein may regulate chondrogenesis by inhibiting transforming growth factor-beta 1-induced gene expression in cartilage. This protein also binds collagen and calcium and may induce collagen mineralization. Polymorphisms in the aspartic acid repeat region of this gene are associated with a susceptibility to osteoarthritis, and also with intervertebral disc disease. Alternative splicing of this gene results in multiple transcript variants.[provided by RefSeq, Jul 2014]

ASPN links:

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

CENPP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3 link	c.564+94919_564+94927delATCATCATC		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1	Q6IPU0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPN	ENST00000375544.7 link	c.147_155delTGATGATGA	p.Asp49_Asp51del	disruptive_inframe_deletion	Exon 2 of 8	1		ENSP00000364694.3		Q9BXN1
CENPP	ENST00000375587.8 link	c.564+94919_564+94927delATCATCATC		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3		Q6IPU0-1

Frequencies

GnomAD3 genomes

AF:

0.000346

AC:

AN:

147582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.000874

Gnomad EAS

AF:

0.000600

Gnomad SAS

AF:

0.000219

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000432

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000384

AC:

532

AN:

1385966

Hom.:

AF XY:

0.000368

AC XY:

254

AN XY:

690112

show subpopulations

African (AFR)

AF:

0.000716

AC:

AN:

30716

American (AMR)

AF:

0.000390

AC:

AN:

41056

Ashkenazi Jewish (ASJ)

AF:

0.000724

AC:

AN:

24870

East Asian (EAS)

AF:

0.000400

AC:

AN:

37488

South Asian (SAS)

AF:

0.000307

AC:

AN:

81542

European-Finnish (FIN)

AF:

0.0000792

AC:

AN:

50512

Middle Eastern (MID)

AF:

0.000359

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.000390

AC:

412

AN:

1056738

Other (OTH)

AF:

0.000313

AC:

AN:

57470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000346

AC:

AN:

147582

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

AN XY:

71678

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

39564

American (AMR)

AF:

0.000136

AC:

AN:

14670

Ashkenazi Jewish (ASJ)

AF:

0.000874

AC:

AN:

3432

East Asian (EAS)

AF:

0.000600

AC:

AN:

5002

South Asian (SAS)

AF:

0.000219

AC:

AN:

4568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000432

AC:

AN:

67174

Other (OTH)

AF:

0.00

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.5

Mutation Taster

=187/13

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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9-92474742-CTCATCATCATCATCATCATCATCA-CTCATCATCATCATCA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over