Genetic Variant COL9A3:c.1008+10C>T (chr20-62828986-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001853.4(COL9A3):c.1008+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,596,078 control chromosomes in the GnomAD database, including 190,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25685 hom., cov: 34)

Exomes 𝑓: 0.47 ( 164801 hom. )

Consequence

COL9A3
NM_001853.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.75

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 20-62828986-C-T is Benign according to our data. Variant chr20-62828986-C-T is described in ClinVar as [Benign]. Clinvar id is 258402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62828986-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.1008+10C>T		intron_variant	Intron 19 of 31	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.1008+10C>T		intron_variant	Intron 19 of 31		NM_001853.4	ENSP00000496793.1		Q14050
COL9A3	ENST00000463487.2 link	n.*10C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84996

AN:

152004

Hom.:

25621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.542

GnomAD3 exomes

AF:

0.527

AC:

116053

AN:

220066

Hom.:

31494

AF XY:

0.519

AC XY:

62815

AN XY:

120944

show subpopulations

Gnomad AFR exome

AF:

0.807

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.765

Gnomad SAS exome

AF:

0.543

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.471

AC:

680780

AN:

1443956

Hom.:

164801

Cov.:

AF XY:

0.472

AC XY:

338721

AN XY:

717432

show subpopulations

Gnomad4 AFR exome

AF:

0.808

Gnomad4 AMR exome

AF:

0.543

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.750

Gnomad4 SAS exome

AF:

0.535

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.443

Gnomad4 OTH exome

AF:

0.498

GnomAD4 genome

AF:

0.560

AC:

85121

AN:

152122

Hom.:

25685

Cov.:

AF XY:

0.559

AC XY:

41542

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.790

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.755

Gnomad4 SAS

AF:

0.548

Gnomad4 FIN

AF:

0.467

Gnomad4 NFE

AF:

0.438

Gnomad4 OTH

AF:

0.548

Alfa

AF:

0.484

Hom.:

3318

Bravo

AF:

0.575

Asia WGS

AF:

0.653

AC:

2270

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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

- -

Genome Diagnostics Laboratory, Amsterdam University 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

- -

May 19, 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. -

not provided

Benign:2

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

-0.90

CADD

Benign

0.067

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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