9-92466381-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_017680.6(ASPN):c.578G>T(p.Gly193Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,606,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G193E) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ASPN
NM_017680.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.863

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017680.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASPN	NM_017680.6	MANE Select	c.578G>T	p.Gly193Val	missense	Exon 4 of 8	NP_060150.4
CENPP	NM_001012267.3	MANE Select	c.564+86522C>A		intron	N/A	NP_001012267.1	Q6IPU0-1
ASPN	NM_001193335.3		c.578G>T	p.Gly193Val	missense	Exon 4 of 6	NP_001180264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASPN	ENST00000375544.7	TSL:1	c.578G>T	p.Gly193Val	missense	Exon 4 of 8	ENSP00000364694.3	Q9BXN1
CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+86522C>A		intron	N/A	ENSP00000364737.3	Q6IPU0-1
ASPN	ENST00000907468.1		c.578G>T	p.Gly193Val	missense	Exon 5 of 9	ENSP00000577527.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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:

0.00000399

AC:

AN:

250764

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1453942

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33340

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.000202

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105036

Other (OTH)

AF:

0.00

AC:

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.44

MutationAssessor

Pathogenic

3.9

PhyloP100

7.6

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-6.9

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.91

MutPred

0.47

Loss of helix (P = 0.0558)

MVP

0.98

MPC

0.85

ClinPred

1.0

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.95

Mutation Taster

=17/83

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over