20-62817617-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001853.4(COL9A3):c.129C>T(p.Pro43Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 1,545,136 control chromosomes in the GnomAD database, including 5,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 631 hom., cov: 33)

Exomes 𝑓: 0.053 ( 4443 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.93

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 20-62817617-C-T is Benign according to our data. Variant chr20-62817617-C-T is described in ClinVar as [Benign]. Clinvar id is 195155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62817617-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.129C>T	p.Pro43Pro	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.129C>T	p.Pro43Pro	synonymous_variant	Exon 2 of 32		NM_001853.4	ENSP00000496793.1	Q14050
COL9A3	ENST00000477612.5 link	n.125C>T		non_coding_transcript_exon_variant	Exon 2 of 12	3
COL9A3	ENST00000489045.5 link	n.175C>T		non_coding_transcript_exon_variant	Exon 1 of 14	5
COL9A3	ENST00000452372.2 link	c.-217C>T		upstream_gene_variant		5		ENSP00000394280.1	Q4VXW1

Frequencies

GnomAD3 genomes

AF:

0.0638

AC:

9714

AN:

152172

Hom.:

632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0495

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0444

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0746

GnomAD3 exomes

AF:

0.104

AC:

14700

AN:

141398

Hom.:

1377

AF XY:

0.104

AC XY:

7975

AN XY:

76530

show subpopulations

Gnomad AFR exome

AF:

0.0493

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.0514

Gnomad EAS exome

AF:

0.355

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0381

Gnomad OTH exome

AF:

0.0774

GnomAD4 exome

AF:

0.0534

AC:

74338

AN:

1392846

Hom.:

4443

Cov.:

AF XY:

0.0561

AC XY:

38557

AN XY:

686836

show subpopulations

Gnomad4 AFR exome

AF:

0.0488

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.0473

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.0455

Gnomad4 NFE exome

AF:

0.0333

Gnomad4 OTH exome

AF:

0.0698

GnomAD4 genome

AF:

0.0639

AC:

9724

AN:

152290

Hom.:

631

Cov.:

AF XY:

0.0680

AC XY:

5063

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0500

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0495

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0444

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0781

Alfa

AF:

0.0430

Hom.:

147

Bravo

AF:

0.0684

Asia WGS

AF:

0.221

AC:

768

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 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. -

Oct 20, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.34

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

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