chr20-62817581-C-A

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.93C>A(p.Pro31Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 1,539,566 control chromosomes in the GnomAD database, including 6,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1252 hom., cov: 33)

Exomes 𝑓: 0.077 ( 5421 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0150

Publications

11 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=-0.66).

BP6

Variant 20-62817581-C-A is Benign according to our data. Variant chr20-62817581-C-A is described in CliVar as Benign. Clinvar id is 195154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62817581-C-A is described in CliVar as Benign. Clinvar id is 195154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62817581-C-A is described in CliVar as Benign. Clinvar id is 195154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62817581-C-A is described in CliVar as Benign. Clinvar id is 195154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62817581-C-A is described in CliVar as Benign. Clinvar id is 195154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.93C>A	p.Pro31Pro	synonymous_variant	Exon 2 of 32	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL9A3	ENST00000649368.1 link	c.93C>A	p.Pro31Pro	synonymous_variant	Exon 2 of 32		NM_001853.4	ENSP00000496793.1	Q14050
COL9A3	ENST00000477612.5 link	n.89C>A		non_coding_transcript_exon_variant	Exon 2 of 12	3
COL9A3	ENST00000489045.5 link	n.139C>A		non_coding_transcript_exon_variant	Exon 1 of 14	5
COL9A3	ENST00000452372.2 link	c.-253C>A		upstream_gene_variant		5		ENSP00000394280.1	Q4VXW1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17559

AN:

151698

Hom.:

1248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.0940

Gnomad FIN

AF:

0.0895

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.110

AC:

15857

AN:

143678

AF XY:

0.106

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.0843

Gnomad NFE exome

AF:

0.0683

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.0773

AC:

107298

AN:

1387750

Hom.:

5421

Cov.:

AF XY:

0.0774

AC XY:

52982

AN XY:

684142

show subpopulations

African (AFR)

AF:

0.184

AC:

5776

AN:

31450

American (AMR)

AF:

0.137

AC:

4853

AN:

35550

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

2817

AN:

25098

East Asian (EAS)

AF:

0.270

AC:

9624

AN:

35608

South Asian (SAS)

AF:

0.0900

AC:

6947

AN:

77218

European-Finnish (FIN)

AF:

0.0810

AC:

3858

AN:

47632

Middle Eastern (MID)

AF:

0.118

AC:

637

AN:

5392

European-Non Finnish (NFE)

AF:

0.0628

AC:

67308

AN:

1072226

Other (OTH)

AF:

0.0951

AC:

5478

AN:

57576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

4460

8920

13380

17840

22300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2668

5336

8004

10672

13340

<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:

0.116

AC:

17601

AN:

151816

Hom.:

1252

Cov.:

AF XY:

0.117

AC XY:

8709

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.182

AC:

7547

AN:

41522

American (AMR)

AF:

0.132

AC:

2013

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3466

East Asian (EAS)

AF:

0.272

AC:

1400

AN:

5148

South Asian (SAS)

AF:

0.0941

AC:

439

AN:

4666

European-Finnish (FIN)

AF:

0.0895

AC:

950

AN:

10618

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0664

AC:

4506

AN:

67830

Other (OTH)

AF:

0.131

AC:

275

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

797

1593

2390

3186

3983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0787

Hom.:

315

Bravo

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 15, 2017

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 30, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.66

CADD

Benign

2.9

(source)

DANN

Benign

0.77

PhyloP100

0.015

PromoterAI

-0.0034

Neutral

(source)

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)

0.020

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