ENST00000375544.7:c.578G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000375544.7(ASPN):c.578G>A(p.Gly193Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,605,986 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0075 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 82 hom. )

Consequence

ASPN
ENST00000375544.7 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.57

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019685864).

BP6

Variant 9-92466381-C-T is Benign according to our data. Variant chr9-92466381-C-T is described in ClinVar as [Benign]. Clinvar id is 3041357.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3 link	c.564+86522C>T		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1	Q6IPU0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASPN	ENST00000375544.7 link	c.578G>A	p.Gly193Glu	missense_variant	Exon 4 of 8	1		ENSP00000364694.3	Q9BXN1
CENPP	ENST00000375587.8 link	c.564+86522C>T		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3	Q6IPU0-1
ASPN	ENST00000375543.2 link	c.578G>A	p.Gly193Glu	missense_variant	Exon 4 of 6	2		ENSP00000364693.1	Q5TBF2
ASPN	ENST00000650794.1 link	n.387+4288G>A		intron_variant	Intron 3 of 5			ENSP00000499088.1	A0A494C1J0

Frequencies

GnomAD3 genomes

AF:

0.00748

AC:

1138

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00963

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00740

AC:

1856

AN:

250764

Hom.:

AF XY:

0.00798

AC XY:

1082

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.00939

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00557

GnomAD4 exome

AF:

0.00929

AC:

13513

AN:

1453794

Hom.:

Cov.:

AF XY:

0.00921

AC XY:

6663

AN XY:

723758

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00385

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00450

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00706

GnomAD4 genome

AF:

0.00746

AC:

1136

AN:

152192

Hom.:

Cov.:

AF XY:

0.00742

AC XY:

552

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00963

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00667

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00735

AC:

892

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ASPN-related disorder

Benign:1

May 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.020

T;T

MetaSVM

Uncertain

-0.072

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-6.0

D;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;P

Vest4

0.90

MVP

0.97

MPC

0.86

ClinPred

0.052

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over