rs2249903

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001853.4(COL9A3):c.909G>A(p.Pro303Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,612,788 control chromosomes in the GnomAD database, including 21,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1394 hom., cov: 35)

Exomes 𝑓: 0.16 ( 19882 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.89

Variant links:

Genes affected

COL9A3 (HGNC:2219): (collagen type IX alpha 3 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. Mutations in this gene are associated with multiple epiphyseal dysplasia type 3. [provided by RefSeq, Jan 2010]

COL9A3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 20-62828772-G-A is Benign according to our data. Variant chr20-62828772-G-A is described in ClinVar as [Benign]. Clinvar id is 258437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62828772-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.909G>A	p.Pro303Pro	synonymous_variant	Exon 18 of 32	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.909G>A	p.Pro303Pro	synonymous_variant	Exon 18 of 32		NM_001853.4	ENSP00000496793.1		Q14050
COL9A3	ENST00000463487.2 link	n.617G>A		non_coding_transcript_exon_variant	Exon 10 of 11	5

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19102

AN:

152198

Hom.:

1395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0568

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0991

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0355

Gnomad SAS

AF:

0.0915

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.129

AC:

32242

AN:

249472

Hom.:

2557

AF XY:

0.133

AC XY:

17978

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.0557

Gnomad AMR exome

AF:

0.0653

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.0343

Gnomad SAS exome

AF:

0.0911

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.159

AC:

232403

AN:

1460472

Hom.:

19882

Cov.:

AF XY:

0.158

AC XY:

114648

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.0524

Gnomad4 AMR exome

AF:

0.0694

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0283

Gnomad4 SAS exome

AF:

0.0922

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.125

AC:

19098

AN:

152316

Hom.:

1394

Cov.:

AF XY:

0.124

AC XY:

9255

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0567

Gnomad4 AMR

AF:

0.0991

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0351

Gnomad4 SAS

AF:

0.0918

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.145

Hom.:

1114

Bravo

AF:

0.115

Asia WGS

AF:

0.0510

AC:

179

AN:

3478

EpiCase

AF:

0.163

EpiControl

AF:

0.171

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Epiphyseal dysplasia, multiple, 3

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.6

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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