ENST00000375544.7:c.89T>C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The ENST00000375544.7(ASPN):c.89T>C(p.Met30Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ASPN
ENST00000375544.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.65

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024217635).

BP6

Variant 9-92474809-A-G is Benign according to our data. Variant chr9-92474809-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3048941.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3 link	c.564+94950A>G		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.89T>C	p.Met30Thr	missense_variant	Exon 2 of 8	1		ENSP00000364694.3		Q9BXN1
CENPP	ENST00000375587.8 link	c.564+94950A>G		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3		Q6IPU0-1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000383

AC:

AN:

248164

Hom.:

AF XY:

0.000268

AC XY:

AN XY:

134286

show subpopulations

Gnomad AFR exome

AF:

0.00492

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000118

AC:

172

AN:

1461730

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00409

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.00145

AC:

220

AN:

152150

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

112

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00482

Gnomad4 AMR

AF:

0.000917

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000156

Hom.:

Bravo

AF:

0.00149

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000412

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ASPN-related disorder

Benign:1

Apr 28, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

Pathogenic

0.67

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.23

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.050

T;T

Polyphen

0.99

D;D

Vest4

0.89

MVP

0.94

MPC

0.80

ClinPred

0.089

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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