rs2249903

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. P303P) has been classified as Likely 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

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

epiphyseal dysplasia, multiple, 3
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
Stickler syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen
Stickler syndrome, type 6
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple epiphyseal dysplasia due to collagen 9 anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Stickler syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL9A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 258437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	NM_001853.4	MANE Select	c.909G>A	p.Pro303Pro	synonymous	Exon 18 of 32	NP_001844.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	ENST00000649368.1	MANE Select	c.909G>A	p.Pro303Pro	synonymous	Exon 18 of 32	ENSP00000496793.1
	COL9A3	ENST00000463487.2	TSL:5	n.617G>A		non_coding_transcript_exon	Exon 10 of 11

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

GnomAD2 exomes

AF:

0.129

AC:

32242

AN:

249472

AF XY:

0.133

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 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

African (AFR)

AF:

0.0524

AC:

1753

AN:

33480

American (AMR)

AF:

0.0694

AC:

3104

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3252

AN:

26130

East Asian (EAS)

AF:

0.0283

AC:

1122

AN:

39696

South Asian (SAS)

AF:

0.0922

AC:

7953

AN:

86252

European-Finnish (FIN)

AF:

0.193

AC:

10047

AN:

52182

Middle Eastern (MID)

AF:

0.137

AC:

793

AN:

5768

European-Non Finnish (NFE)

AF:

0.176

AC:

195794

AN:

1111892

Other (OTH)

AF:

0.142

AC:

8585

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

11930

23860

35791

47721

59651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6724

13448

20172

26896

33620

<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:

0.125

AC:

19098

AN:

152316

Hom.:

1394

Cov.:

AF XY:

0.124

AC XY:

9255

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0567

AC:

2356

AN:

41584

American (AMR)

AF:

0.0991

AC:

1517

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

429

AN:

3472

East Asian (EAS)

AF:

0.0351

AC:

182

AN:

5178

South Asian (SAS)

AF:

0.0918

AC:

443

AN:

4828

European-Finnish (FIN)

AF:

0.195

AC:

2071

AN:

10618

Middle Eastern (MID)

AF:

0.151

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.172

AC:

11687

AN:

68006

Other (OTH)

AF:

0.134

AC:

284

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

897

1794

2692

3589

4486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.145

Hom.:

1236

Bravo

AF:

0.115

Asia WGS

AF:

0.0510

AC:

179

AN:

3478

EpiCase

AF:

0.163

EpiControl

AF:

0.171

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (3)

Epiphyseal dysplasia, multiple, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.6

(source)

DANN

Benign

0.88

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over