20-62840573-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001853.4(COL9A3):c.1896C>T(p.Asp632Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,612,582 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 33)

Exomes 𝑓: 0.013 ( 162 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.91

Publications

2 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=-0.56).

BP6

Variant 20-62840573-C-T is Benign according to our data. Variant chr20-62840573-C-T is described in ClinVar as Benign. ClinVar VariationId is 258419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00774 (1179/152342) while in subpopulation NFE AF = 0.0138 (941/68030). AF 95% confidence interval is 0.0131. There are 9 homozygotes in GnomAd4. There are 536 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AD,AR gene

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.1896C>T	p.Asp632Asp	synonymous	Exon 32 of 32	NP_001844.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL9A3	ENST00000649368.1	MANE Select	c.1896C>T	p.Asp632Asp	synonymous	Exon 32 of 32	ENSP00000496793.1
COL9A3	ENST00000467819.5	TSL:1	n.407C>T		non_coding_transcript_exon	Exon 4 of 4
COL9A3	ENST00000934236.1		c.1947C>T	p.Asp649Asp	synonymous	Exon 33 of 33	ENSP00000604295.1

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1179

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00690

AC:

1720

AN:

249354

AF XY:

0.00663

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00722

GnomAD4 exome

AF:

0.0131

AC:

19061

AN:

1460240

Hom.:

162

Cov.:

AF XY:

0.0127

AC XY:

9208

AN XY:

726484

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

33442

American (AMR)

AF:

0.00391

AC:

175

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26124

East Asian (EAS)

AF:

0.000151

AC:

AN:

39694

South Asian (SAS)

AF:

0.00229

AC:

197

AN:

86202

European-Finnish (FIN)

AF:

0.00300

AC:

159

AN:

52962

Middle Eastern (MID)

AF:

0.00180

AC:

AN:

5006

European-Non Finnish (NFE)

AF:

0.0161

AC:

17868

AN:

1111804

Other (OTH)

AF:

0.00934

AC:

563

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

989

1978

2967

3956

4945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.00774

AC:

1179

AN:

152342

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

536

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00238

AC:

AN:

41586

American (AMR)

AF:

0.00529

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0138

AC:

941

AN:

68030

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.0113

Hom.:

Bravo

AF:

0.00764

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0137

EpiControl

AF:

0.0105

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Connective tissue disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.13

(source)

DANN

Benign

0.83

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

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