20-62837219-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001853.4(COL9A3):c.1740T>C(p.Pro580Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,611,778 control chromosomes in the GnomAD database, including 387,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43619 hom., cov: 32)

Exomes 𝑓: 0.68 ( 343494 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.940

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 20-62837219-T-C is Benign according to our data. Variant chr20-62837219-T-C is described in ClinVar as Benign. ClinVar VariationId is 258417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.1740T>C	p.Pro580Pro	synonymous_variant	Exon 30 of 32	ENST00000649368.1	NP_001844.3	Q14050
COL9A3	XM_047439893.1 link	c.1917T>C	p.Pro639Pro	synonymous_variant	Exon 29 of 31		XP_047295849.1
COL9A3	XM_047439894.1 link	c.1179T>C	p.Pro393Pro	synonymous_variant	Exon 30 of 32		XP_047295850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.1740T>C	p.Pro580Pro	synonymous_variant	Exon 30 of 32		NM_001853.4	ENSP00000496793.1		Q14050

Frequencies

GnomAD3 genomes

AF:

0.748

AC:

113705

AN:

151936

Hom.:

43553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.699

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.568

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.687

Gnomad OTH

AF:

0.733

GnomAD2 exomes

AF:

0.681

AC:

168289

AN:

247034

AF XY:

0.674

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.664

Gnomad ASJ exome

AF:

0.712

Gnomad EAS exome

AF:

0.598

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.683

GnomAD4 exome

AF:

0.684

AC:

998414

AN:

1459724

Hom.:

343494

Cov.:

AF XY:

0.681

AC XY:

494259

AN XY:

726294

show subpopulations

African (AFR)

AF:

0.939

AC:

31449

AN:

33476

American (AMR)

AF:

0.668

AC:

29847

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

18552

AN:

26110

East Asian (EAS)

AF:

0.603

AC:

23923

AN:

39696

South Asian (SAS)

AF:

0.593

AC:

51183

AN:

86244

European-Finnish (FIN)

AF:

0.682

AC:

35158

AN:

51570

Middle Eastern (MID)

AF:

0.747

AC:

4294

AN:

5746

European-Non Finnish (NFE)

AF:

0.685

AC:

762031

AN:

1111822

Other (OTH)

AF:

0.695

AC:

41977

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18836

37672

56507

75343

94179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19458

38916

58374

77832

97290

<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:

0.749

AC:

113837

AN:

152054

Hom.:

43619

Cov.:

AF XY:

0.742

AC XY:

55166

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.929

AC:

38568

AN:

41522

American (AMR)

AF:

0.699

AC:

10683

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

2528

AN:

3466

East Asian (EAS)

AF:

0.593

AC:

3046

AN:

5134

South Asian (SAS)

AF:

0.569

AC:

2739

AN:

4810

European-Finnish (FIN)

AF:

0.681

AC:

7200

AN:

10576

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.687

AC:

46672

AN:

67942

Other (OTH)

AF:

0.733

AC:

1549

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1431

2862

4293

5724

7155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.698

Hom.:

20566

Bravo

AF:

0.762

Asia WGS

AF:

0.651

AC:

2266

AN:

3478

EpiCase

AF:

0.694

EpiControl

AF:

0.695

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.75

CADD

Benign

0.79

(source)

DANN

Benign

0.54

PhyloP100

-0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over